179 results on '"Al-Herz, W."'
Search Results
2. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015
- Author
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Puck, Jennifer, Picard, C, Al-Herz, W, Bousfiha, A, Casanova, JL, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Holland, SM, and Klein, C
- Abstract
© 2015, The Author(s).We report the updated classification of primary immunodeficiencies compiled by the Primary Immunodeficiency Expert Committee (PID EC) of the International Union of Immunological Societies (IUIS). In the two years since the previous ve
- Published
- 2015
3. The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies
- Author
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Puck, Jennifer, Bousfiha, A, Jeddane, L, Al-Herz, W, Ailal, F, Casanova, J, Chatila, T, Conley, ME, Cunningham, C, Etzioni, A, and Franco, JL
- Abstract
© 2015 Springer Science+Business Media New York There are now nearly 300 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. For each of these five categories, a gr
- Published
- 2015
4. Corrigendum: Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency.
- Author
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Al-Herz, W, Bousfiha, A, Casanova, JL, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Franco, JL, Gaspar, HB, Holland, SM, Klein, C, Nonoyama, S, Ochs, HD, Oksenhendler, E, Picard, C, Puck, JM, Sullivan, K, and Tang, ML
- Subjects
IUIS ,classification ,gene defects ,genotype ,immunodeficiency ,Immunology - Abstract
[This corrects the article on p. 162 in vol. 5, PMID: 24795713.].
- Published
- 2014
5. Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome
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Rigoni, R, Fontana, E, Dobbs, K, Marrella, V, Taverniti, V, Maina, V, Facoetti, A, D'Amico, G, Al-Herz, W, Cruz-Munoz, M, Schuetz, C, Gennery, A, Garabedian, E, Giliani, S, Draper, D, Dbaibo, G, Geha, R, Meyts, I, Tousseyn, T, Neven, B, Moshous, D, Fischer, A, Schulz, A, Finocchi, A, Kuhns, D, Fink, D, Lionakis, M, Swamydas, M, Guglielmetti, S, Alejo, J, Myles, I, Pittaluga, S, Notarangelo, L, Villa, A, Cassani, B, Rigoni R., Fontana E., Dobbs K., Marrella V., Taverniti V., Maina V., Facoetti A., D'Amico G., Al-Herz W., Cruz-Munoz M. E., Schuetz C., Gennery A. R., Garabedian E. K., Giliani S., Draper D., Dbaibo G., Geha R. S., Meyts I., Tousseyn T., Neven B., Moshous D., Fischer A., Schulz A., Finocchi A., Kuhns D. B., Fink D. L., Lionakis M. S., Swamydas M., Guglielmetti S., Alejo J., Myles I. A., Pittaluga S., Notarangelo L. D., Villa A., Cassani B., Rigoni, R, Fontana, E, Dobbs, K, Marrella, V, Taverniti, V, Maina, V, Facoetti, A, D'Amico, G, Al-Herz, W, Cruz-Munoz, M, Schuetz, C, Gennery, A, Garabedian, E, Giliani, S, Draper, D, Dbaibo, G, Geha, R, Meyts, I, Tousseyn, T, Neven, B, Moshous, D, Fischer, A, Schulz, A, Finocchi, A, Kuhns, D, Fink, D, Lionakis, M, Swamydas, M, Guglielmetti, S, Alejo, J, Myles, I, Pittaluga, S, Notarangelo, L, Villa, A, Cassani, B, Rigoni R., Fontana E., Dobbs K., Marrella V., Taverniti V., Maina V., Facoetti A., D'Amico G., Al-Herz W., Cruz-Munoz M. E., Schuetz C., Gennery A. R., Garabedian E. K., Giliani S., Draper D., Dbaibo G., Geha R. S., Meyts I., Tousseyn T., Neven B., Moshous D., Fischer A., Schulz A., Finocchi A., Kuhns D. B., Fink D. L., Lionakis M. S., Swamydas M., Guglielmetti S., Alejo J., Myles I. A., Pittaluga S., Notarangelo L. D., Villa A., and Cassani B.
- Abstract
Background: Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). Objective: The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. Methods: We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2R229Q/R229Q (Rag2R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. Results: We show that memory/activated T cells from patients with OS and from the Rag2R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad TH1/TH2/TH17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q mice results in increased frequency of Ccr4+ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by TH1 effector T cells. Conclusions: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS.
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- 2020
6. Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency
- Author
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Aydin, S.E., Freeman, A.F., Al-Herz, W., Al-Mousa, H.A., Arnaout, R.K., Aydin, R.C., Barlogis, V., Belohradsky, B.H., Bonfim, C., Bredius, R.G., Chu, J.I., Ciocarlie, O.C., Dogu, F., Gaspar, H.B., Geha, R.S., Gennery, A.R., Hauck, F., Hawwari, A., Hickstein, D.D., Hoenig, M., Ikinciogullari, A., Klein, C., Kumar, A., Ifversen, M.R.S., Matthes, S., Metin, A., Neven, B., Pai, S.Y., Parikh, S.H., Picard, C., Renner, E.D., Sanal, O., Schulz, A.S., Schuster, F., Shah, N.N., Shereck, E.B., Slatter, M.A., Su, H.C., Montfrans, J. van, Woessmann, W., Ziegler, J.B., Albert, M.H., Inborn Errors Working Party Europe, and European Soc Primary Immunodefici
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,DOCK8 deficiency ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Kaplan-Meier Estimate ,Treosulfan ,Article ,Young Adult ,Internal medicine ,medicine ,Journal Article ,Immunology and Allergy ,Guanine Nucleotide Exchange Factors ,Humans ,Child ,Immunodeficiency ,business.industry ,Hematopoietic Stem Cell Transplantation ,Immunologic Deficiency Syndromes ,Infant ,Retrospective cohort study ,medicine.disease ,Combined immunodeficiency ,Regimen ,Graft-versus-host disease ,surgical procedures, operative ,Child, Preschool ,Failure to thrive ,HSCT ,Female ,medicine.symptom ,business ,Busulfan ,medicine.drug - Abstract
BACKGROUND: Biallelic variations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency with eczema, recurrent bacterial and viral infections, and malignancy. Natural disease outcome is dismal, but allogeneic hematopoietic stem cell transplantation (HSCT) can cure the disease.OBJECTIVE: To determine outcome of HSCT for DOCK8 deficiency and define possible outcome variables.METHODS: We performed a retrospective study of the results of HSCT in a large international cohort of DOCK8-deficient patients.RESULTS: We identified 81 patients from 22 centers transplanted at a median age of 9.7 years (range, 0.7-27.2 years) between 1995 and 2015. After median follow-up of 26 months (range, 3-135 months), 68 (84%) patients are alive. Severe acute (III-IV) or chronic graft versus host disease occurred in 11% and 10%, respectively. Causes of death were infections (n = 5), graft versus host disease (5), multiorgan failure (2), and preexistent lymphoma (1). Survival after matched related (n = 40) or unrelated (35) HSCT was 89% and 81%, respectively. Reduced-toxicity conditioning based on either treosulfan or reduced-dose busulfan resulted in superior survival compared with fully myeloablative busulfan-based regimens (97% vs 78%; P = .049). Ninety-six percent of patients younger than 8 years at HSCT survived, compared with 78% of those 8 years and older (P = .06). Of the 73 patients with chimerism data available, 65 (89%) had more than 90% donor T-cell chimerism at last follow-up. Not all disease manifestations responded equally well to HSCT: eczema, infections, and mollusca resolved quicker than food allergies or failure to thrive.CONCLUSIONS: HSCT is curative in most DOCK8-deficient patients, confirming this approach as the treatment of choice. HSCT using a reduced-toxicity regimen may offer the best chance for survival. (C) 2018 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology
- Published
- 2019
7. Outcomes and Treatment Strategies for Autoimmunity and Hyperinflammation in Patients with RAG Deficiency
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Farmer, J.R. Foldvari, Z. Ujhazi, B. De Ravin, S.S. Chen, K. Bleesing, J.J.H. Schuetz, C. Al-Herz, W. Abraham, R.S. Joshi, A.Y. Costa-Carvalho, B.T. Buchbinder, D. Booth, C. Reiff, A. Ferguson, P.J. Aghamohammadi, A. Abolhassani, H. Puck, J.M. Adeli, M. Cancrini, C. Palma, P. Bertaina, A. Locatelli, F. Di Matteo, G. Geha, R.S. Kanariou, M.G. Lycopoulou, L. Tzanoudaki, M. Sleasman, J.W. Parikh, S. Pinero, G. Fischer, B.M. Dbaibo, G. Unal, E. Patiroglu, T. Karakukcu, M. Al-Saad, K.K. Dilley, M.A. Pai, S.-Y. Dutmer, C.M. Gelfand, E.W. Geier, C.B. Eibl, M.M. Wolf, H.M. Henderson, L.A. Hazen, M.M. Bonfim, C. Wolska-Kuśnierz, B. Butte, M.J. Hernandez, J.D. Nicholas, S.K. Stepensky, P. Chandrakasan, S. Miano, M. Westermann-Clark, E. Goda, V. Kriván, G. Holland, S.M. Fadugba, O. Henrickson, S.E. Ozen, A. Karakoc-Aydiner, E. Baris, S. Kiykim, A. Bredius, R. Hoeger, B. Boztug, K. Pashchenko, O. Neven, B. Moshous, D. de Villartay, J.-P. Bousfiha, A.A. Hill, H.R. Notarangelo, L.D. Walter, J.E.
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hemic and lymphatic diseases - Abstract
Background: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. Objective: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. Methods: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. Results: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. Conclusions: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management. © 2019 The Authors
- Published
- 2019
8. X-linked agammaglobulinemia (XLA): Phenotype, diagnosis, and therapeutic challenges around the world
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El-Sayed, ZA, Abramova, I, Carlos Aldave, J, Al-Herz, W, Bezrodnik, L, Boukari, R, Bousfiha, AA, Cancrini, C, Condino-Neto, A, Dbaibo, G, Derfalvi, B, Dogu, F, Edgar, JDM, Eley, B, El-Owaidy, RH, Elva Espinosa-Padilla, S, Galal, N, Haerynck, F, Hanna-Wakim, R, Hossny, E, Ikinciogullari, A, Kamal, E, Kanegane, H, Kechout, N, Lau, YL, Morio, T, Moschese, V, Neves, JF, Ouederni, M, Paganelli, R, Paris, K, Pignata, C, Plebani, A, Qamar, FN, Qureshi, S, Radhakrishnan, N, Rezaei, N, Rosario, N, Routes, J, Sanchez, B, Sediva, A, Seppanen, MRJ, Serrano, EG, Shcherbina, A, Singh, S, Siniah, S, Spadaro, G, Tang, M, Maria Vinet, A, Volokha, A, Sullivan, KE, El-Sayed, ZA, Abramova, I, Carlos Aldave, J, Al-Herz, W, Bezrodnik, L, Boukari, R, Bousfiha, AA, Cancrini, C, Condino-Neto, A, Dbaibo, G, Derfalvi, B, Dogu, F, Edgar, JDM, Eley, B, El-Owaidy, RH, Elva Espinosa-Padilla, S, Galal, N, Haerynck, F, Hanna-Wakim, R, Hossny, E, Ikinciogullari, A, Kamal, E, Kanegane, H, Kechout, N, Lau, YL, Morio, T, Moschese, V, Neves, JF, Ouederni, M, Paganelli, R, Paris, K, Pignata, C, Plebani, A, Qamar, FN, Qureshi, S, Radhakrishnan, N, Rezaei, N, Rosario, N, Routes, J, Sanchez, B, Sediva, A, Seppanen, MRJ, Serrano, EG, Shcherbina, A, Singh, S, Siniah, S, Spadaro, G, Tang, M, Maria Vinet, A, Volokha, A, and Sullivan, KE
- Abstract
BACKGROUND: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features. METHODS: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries. RESULTS: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to rep
- Published
- 2019
9. Outcomes and Treatment Strategies for Autoimmunity and Hyperinflammation in Patients with RAG Deficiency
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Farmer, J. R., Foldvari, Z., Ujhazi, B., De Ravin, S. S., Chen, K., Bleesing, J. J. H., Schuetz, C., Al-Herz, W., Abraham, R. S., Joshi, A. Y., Costa-Carvalho, B. T., Buchbinder, D., Booth, C., Reiff, A., Ferguson, P. J., Aghamohammadi, A., Abolhassani, H., Puck, J. M., Adeli, M., Cancrini, C., Palma, P., Bertaina, A., Locatelli, Franco, Di Matteo, G., Geha, R. S., Kanariou, M. G., Lycopoulou, L., Tzanoudaki, M., Sleasman, J. W., Parikh, S., Pinero, G., Fischer, B. M., Dbaibo, G., Unal, E., Patiroglu, T., Karakukcu, M., Al-Saad, K. K., Dilley, M. A., Pai, S. -Y., Dutmer, C. M., Gelfand, E. W., Geier, C. B., Eibl, M. M., Wolf, H. M., Henderson, L. A., Hazen, M. M., Bonfim, C., Wolska-Kusnierz, B., Butte, M. J., Hernandez, J. D., Nicholas, S. K., Stepensky, P., Chandrakasan, S., Miano, M., Westermann-Clark, E., Goda, V., Krivan, G., Holland, S. M., Fadugba, O., Henrickson, S. E., Ozen, A., Karakoc-Aydiner, E., Baris, S., Kiykim, A., Bredius, R., Hoeger, B., Boztug, K., Pashchenko, O., Neven, B., Moshous, D., de Villartay, J. -P., Bousfiha, A. A., Hill, H. R., Notarangelo, L. D., Walter, J. E., Locatelli F. (ORCID:0000-0002-7976-3654), Farmer, J. R., Foldvari, Z., Ujhazi, B., De Ravin, S. S., Chen, K., Bleesing, J. J. H., Schuetz, C., Al-Herz, W., Abraham, R. S., Joshi, A. Y., Costa-Carvalho, B. T., Buchbinder, D., Booth, C., Reiff, A., Ferguson, P. J., Aghamohammadi, A., Abolhassani, H., Puck, J. M., Adeli, M., Cancrini, C., Palma, P., Bertaina, A., Locatelli, Franco, Di Matteo, G., Geha, R. S., Kanariou, M. G., Lycopoulou, L., Tzanoudaki, M., Sleasman, J. W., Parikh, S., Pinero, G., Fischer, B. M., Dbaibo, G., Unal, E., Patiroglu, T., Karakukcu, M., Al-Saad, K. K., Dilley, M. A., Pai, S. -Y., Dutmer, C. M., Gelfand, E. W., Geier, C. B., Eibl, M. M., Wolf, H. M., Henderson, L. A., Hazen, M. M., Bonfim, C., Wolska-Kusnierz, B., Butte, M. J., Hernandez, J. D., Nicholas, S. K., Stepensky, P., Chandrakasan, S., Miano, M., Westermann-Clark, E., Goda, V., Krivan, G., Holland, S. M., Fadugba, O., Henrickson, S. E., Ozen, A., Karakoc-Aydiner, E., Baris, S., Kiykim, A., Bredius, R., Hoeger, B., Boztug, K., Pashchenko, O., Neven, B., Moshous, D., de Villartay, J. -P., Bousfiha, A. A., Hill, H. R., Notarangelo, L. D., Walter, J. E., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Background: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. Objective: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. Methods: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. Results: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. Conclusions: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.
- Published
- 2019
10. STAT5b Deficiency: A Rare Cause of Pulmonary Alveolar Proteinosis
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Krone, K., primary, Platt, C., additional, Pai, S.-Y., additional, Forbes, L., additional, Vece, T.J., additional, Al-Herz, W., additional, Carey, B.C., additional, Trapnell, B.C., additional, and Fishman, M.P., additional
- Published
- 2019
- Full Text
- View/download PDF
11. The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies
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Bousfiha, A, Jeddane, L, Picard, C, Ailal, F, Gaspar, HB, Al-Herz, W, Chatila, T, Crow, YJ, Cunningham-Rundles, C, Etzioni, A, Luis Franco, J, Holland, SM, Klein, C, Morio, T, Ochs, HD, Oksenhendler, E, Puck, J, Tang, MLK, Tangye, SG, Torgerson, TR, Casanova, J-L, Sullivan, KE, Bousfiha, A, Jeddane, L, Picard, C, Ailal, F, Gaspar, HB, Al-Herz, W, Chatila, T, Crow, YJ, Cunningham-Rundles, C, Etzioni, A, Luis Franco, J, Holland, SM, Klein, C, Morio, T, Ochs, HD, Oksenhendler, E, Puck, J, Tang, MLK, Tangye, SG, Torgerson, TR, Casanova, J-L, and Sullivan, KE
- Abstract
Since the 1990s, the International Union of Immunological Societies (IUIS) PID expert committee (EC), now called Inborn Errors of Immunity Committee, has published every other year a classification of the inborn errors of immunity. This complete catalog serves as a reference for immunologists and researchers worldwide. However, it was unadapted for clinicians at the bedside. For those, the IUIS PID EC is now publishing a phenotypical classification since 2013, which proved to be more user-friendly. There are now 320 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. We herein propose the revised 2017 phenotypic classification, based on the accompanying 2017 IUIS Inborn Errors of Immunity Committee classification.
- Published
- 2018
12. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity
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Picard, C, Bobby Gaspar, H, Al-Herz, W, Bousfiha, A, Casanova, J-L, Chatila, T, Crow, YJ, Cunningham-Rundles, C, Etzioni, A, Luis Franco, J, Holland, SM, Klein, C, Morio, T, Ochs, HD, Oksenhendler, E, Puck, J, Tang, MLK, Tangye, SG, Torgerson, TR, Sullivan, KE, Picard, C, Bobby Gaspar, H, Al-Herz, W, Bousfiha, A, Casanova, J-L, Chatila, T, Crow, YJ, Cunningham-Rundles, C, Etzioni, A, Luis Franco, J, Holland, SM, Klein, C, Morio, T, Ochs, HD, Oksenhendler, E, Puck, J, Tang, MLK, Tangye, SG, Torgerson, TR, and Sullivan, KE
- Abstract
Beginning in 1970, a committee was constituted under the auspices of the World Health Organization (WHO) to catalog primary immunodeficiencies. Twenty years later, the International Union of Immunological Societies (IUIS) took the remit of this committee. The current report details the categorization and listing of 354 (as of February 2017) inborn errors of immunity. The growth and increasing complexity of the field have been impressive, encompassing an increasing variety of conditions, and the classification described here will serve as a critical reference for immunologists and researchers worldwide.
- Published
- 2018
13. Modeling altered T-cell development with human induced pluripotent stem cells from patients with RAG1 mutations and distinct immunological phenotypes
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Brauer, Pm, Pessach, Im, Clarke, E, Rowe, Jh, Ott de Bruin, L, Lee, Yn, Dominguez Brauer, C, Comeau, Am, Awong, G, Felgentreff, K, Zhang, Yh, Bredemeyer, A, Al Herz, W, Du, L, Ververs, F, Kennedy, M, Giliani, Silvia Clara, Keller, G, Sleckman, Bp, Schatz, Dg, Bushman, Fd, Notarangelo, Ld, and Zúñiga Pflücker, J. c.
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- 2016
14. Decreased somatic hypermutation induces an impaired peripheral B cell tolerance checkpoint
- Author
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Cantaert, T. (Tineke), Schickel, J.-N. (Jean-Nicolas), Bannock, J.M. (Jason M.), Ng, Y.-S. (Yen-Shing), Massad, C. (Christopher), Delmotte, F.R. (Fabien R.), Yamakawa, N. (Natsuko), Glauzy, S. (Salome), Chamberlain, N. (Nicolas), Kinnunen, T. (Tuure), Menard, L. (Laurence), Lavoie, A. (Aubert), Walter, J.E. (Jolan E.), Notarangelo, L.D. (Luigi Daniele), Bruneau, J. (Julie), Al-Herz, W. (Waleed), Kilic, S.S., Ochs, H.D. (Hans D.), Cunningham-Rundles, C. (Charlotte), Burg, M. (Mirjam) van der, Kuijpers, T.W. (Taco W.), Kracker, S. (Sven), Kaneko, H. (Hideo), Sekinaka, Y. (Yujin), Nonoyama, S. (Shigeaki), Durandy, A. (Anne), Meffre, E. (Eric), Cantaert, T. (Tineke), Schickel, J.-N. (Jean-Nicolas), Bannock, J.M. (Jason M.), Ng, Y.-S. (Yen-Shing), Massad, C. (Christopher), Delmotte, F.R. (Fabien R.), Yamakawa, N. (Natsuko), Glauzy, S. (Salome), Chamberlain, N. (Nicolas), Kinnunen, T. (Tuure), Menard, L. (Laurence), Lavoie, A. (Aubert), Walter, J.E. (Jolan E.), Notarangelo, L.D. (Luigi Daniele), Bruneau, J. (Julie), Al-Herz, W. (Waleed), Kilic, S.S., Ochs, H.D. (Hans D.), Cunningham-Rundles, C. (Charlotte), Burg, M. (Mirjam) van der, Kuijpers, T.W. (Taco W.), Kracker, S. (Sven), Kaneko, H. (Hideo), Sekinaka, Y. (Yujin), Nonoyama, S. (Shigeaki), Durandy, A. (Anne), and Meffre, E. (Eric)
- Abstract
Patients with mutations in AICDA, which encodes activation-induced cytidine deaminase (AID), display an impaired peripheral B cell tolerance. AID mediates class-switch recombination (CSR) and somatic hypermutation (SHM) in B cells, but the mechanism by which AID prevents the accumulation of autoreactive B cells in blood is unclear. Here, we analyzed B cell tolerance in AID-deficient patients, patients with autosomal dominant AID mutations (AD-AID), asymptomatic AICDA heterozygotes (AID+/-), and patients with uracil N-glycosylase (UNG) deficiency, which impairs CSR but not SHM. The low frequency of autoreactive mature naive B cells in UNG-deficient patients resembled that of healthy subjects, revealing that impaired CSR does not interfere with the peripheral B cell tolerance checkpoint. In contrast, we observed decreased frequencies of SHM in memory B cells from AD-AID patients and AID+/- subjects, who were unable to prevent the accumulation of autoreactive mature naive B cells. In addition, the individuals with AICDA mutations, but not UNGdeficient patients, displayed Tr
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- 2016
- Full Text
- View/download PDF
15. Corrigendum: Primary immunodeficiency diseases: An update on the classification from the international union of immunological societies expert committee for primary immunodeficiency [Front immunol, 5, (2014), 162] doi:10.3389/fimmu.2014.00162
- Author
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Al-Herz, W, Bousfiha, A, Casanova, JL, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Franco, JL, Gaspar, HB, Holland, SM, Klein, C, Nonoyama, S, Ochs, HD, Oksenhendler, E, Picard, C, Puck, JM, Sullivan, K, and Tang, MLK
- Published
- 2014
16. Sinopulmonary Complications in Subjects With Primary Immunodeficiency
- Author
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Owayed, A., primary and Al-Herz, W., additional
- Published
- 2016
- Full Text
- View/download PDF
17. The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies
- Author
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Bousfiha, A, Jeddane, L, Al-Herz, W, Ailal, F, Casanova, J-L, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Franco, JL, Gaspar, HB, Holland, SM, Klein, C, Nonoyama, S, Ochs, HD, Oksenhendler, E, Picard, C, Puck, JM, Sullivan, KE, Tang, MLK, Bousfiha, A, Jeddane, L, Al-Herz, W, Ailal, F, Casanova, J-L, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Franco, JL, Gaspar, HB, Holland, SM, Klein, C, Nonoyama, S, Ochs, HD, Oksenhendler, E, Picard, C, Puck, JM, Sullivan, KE, and Tang, MLK
- Abstract
There are now nearly 300 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. For each of these five categories, a growing variety of phenotypes are ascribed to Primary Immunodeficiency Diseases (PID), making PIDs a rapidly expanding field of medicine. The International Union of Immunological Societies (IUIS) PID expert committee (EC) has published every other year a classification of these disorders into tables, defined by shared pathogenesis and/or clinical consequences. In 2013, the IUIS committee also proposed a more user-friendly, phenotypic classification, based on the selection of key phenotypes at the bedside. We herein propose the revised figures, based on the accompanying 2015 IUIS PID EC classification.
- Published
- 2015
18. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015
- Author
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Picard, C, Al-Herz, W, Bousfiha, A, Casanova, J-L, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Holland, SM, Klein, C, Nonoyama, S, Ochs, HD, Oksenhendler, E, Puck, JM, Sullivan, KE, Tang, MLK, Franco, JL, Gaspar, HB, Picard, C, Al-Herz, W, Bousfiha, A, Casanova, J-L, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Holland, SM, Klein, C, Nonoyama, S, Ochs, HD, Oksenhendler, E, Puck, JM, Sullivan, KE, Tang, MLK, Franco, JL, and Gaspar, HB
- Abstract
We report the updated classification of primary immunodeficiencies compiled by the Primary Immunodeficiency Expert Committee (PID EC) of the International Union of Immunological Societies (IUIS). In the two years since the previous version, 34 new gene defects are reported in this updated version. For each disorder, the key clinical and laboratory features are provided. In this new version we continue to see the increasing overlap between immunodeficiency, as manifested by infection and/or malignancy, and immune dysregulation, as manifested by auto-inflammation, auto-immunity, and/or allergy. There is also an increased number of genetic defects that lead to susceptibility to specific organisms which reflects the finely tuned nature of immune defense systems. This classification is the most up to date catalogue of all known and published primary immunodeficiencies and acts as a current reference of the knowledge of these conditions and is an important aid for the genetic and molecular diagnosis of patients with these rare diseases.
- Published
- 2015
19. MANAGEMENT OF DOCK8 DEFICIENCY BY HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)
- Author
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Aydin, S., Freeman, A. F., Sanal, O., Al-Mousa, H., Matthes-Martin, S., Cuellar-Rodriguez, J., Hickstein, D. D., Tavil, B., Azik, F. M., Bittner, T. C., Bredius, R. G., Ayvaz, D., Kuskonmaz, B., Hoenig, M., Schulz, A., Picard, C., Barlogis, V., Gennery, A., Ifversen, M., Montfrans, J. M., Kuijpers, T. W., Dueckers, G., Al-Herz, W., Pai, S. Y., Geha, R. S., Notheis, G., Schwarze, C. P., Schuster, F., Gathmann, B., Grimbacher, B., Gaspar, B., Belohradsky, B. H., Ochs, H., Ellen Renner, Chatila, T., Engelhardt, K. R., and Albert, M. H.
- Published
- 2012
20. Dock8 deficiency and a diagnostic score to differentiate it from other Hyper-IGE syndromes
- Author
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Engelhardt, K. R., Gertz, E. M., Keleş, S., Schaeffer, Alejandro A., Ceja, R., Sassi, A., Massaad, M. J., Mellouli, F., Benmustapha, I., Khemiri, M., Etzioni, A., Freeman, A. F., Thiel, J., Schulze, I., Al-Herz, W., Metin, A., Sanal, O., Yeganeh, M., Niehues, T., Siepermann, K., Ünal, E., Patıroğlu, T., Dasouki, M., Yılmaz, Mustafa, Genel, F., Aytekin, C., Kütükçüler, N., Somer, Ayper, Kılıç, M., Reisli, I., Camcıoğlu, Y., Gennery, A. R., Cant, A. J., Jones, A., Gaspar, H. B., Arkwright, P. D., Pietrogrande, M. C., Baz, Z., Al-Tamemi, Salem, Lougaris, V., Lefranc, G., Megarbane, Andre, Boutros, J., Galal, N., Bejaoui, Mohamed, Barbouche, R., Geha, R. S., Chatila, T. A., Grimbacher, B., Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Çocuk İmmünolojisi Bölümü., Kılıç, Sara Şebnem, and AAH-1658-2021
- Subjects
Immunology - Abstract
Bu çalışma, 3-6 Ekim 2012'de Floransa[İtalya]'da düzenlenen 15. Biennial Meeting European-Society-for-Immunodeficiency (ESID)'de bildiri olarak sunulmuştur. European Soc Immunodeficiency (ESID) Int Nursing Grp Immunodeficiencies (INGID) Int Patient Org Primary Immunodeficiencies (IPOPI)
- Published
- 2012
21. CHARACTERIZATION OF AUTOANTIBODY PROFILE AMONG PATIENTS WITH PRIMARY IMMUNODEFICIENCY SECONDARY TO RAG MUTATION
- Author
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Walter, Je, Matthew, D, Lee, Yn, Recher, M, Patrizi, L, Al Herz, W, Cowan, M, Puck, J, Bleesing, J, Filipovich, L, Niehues, T, Schuetz, C, Drucker, G, Malech, H, De Ravin SS, Uzel, G, Facchetti, Fabio, Gennery, A, Alenezi, Hm, Chinen, J, Dbaibo, G, El Ghazali, G, Pasic, S, Chen, K, Nadeau, K, Abraham, R, Giliani, Silvia Clara, Balboni, M, Browne, S, and Notarangelo, Luigi Daniele
- Published
- 2012
22. DOCK8 functions as an adaptor that links TLR-MyD88 signalling to B cell activation
- Author
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Jabara, H. H., Mcdonald, D. R., Janssen, E., Massaad, M. J., Ramesh, N., Borzutzky, A., Rauter, I., Benson, H., Schneider, L., Baxi, S., Recher, M., Notarangelo, L. D., Wakim, R., Dbaibo, G., Dasouki, M., Al Herz, W., Barlan, I., Baris, S., Kutukculer, N., Ochs, H. D., Plebani, Alessandro, Kanariou, M., Lefranc, G., Reisli, I., Fitzgerald, K. A., Golenbock, D., Manis, J., Keles, S., Ceja, R., Chatila, T. A., and Geha, R. S.
- Subjects
DOCK8 ,B cell activation ,Adaptor protein ,TLR-MyD88 signalling - Published
- 2012
23. SP110 REGULATES NUCLEAR ORPHAN RECEPTOR NUR77-DRIVEN APOPTOSIS IN T CELLS
- Author
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Recher, M, Deenick, E, Al Herz, W, Frugoni, F, Lee, Y, Delmonte, Om, Giliani, Silvia Clara, Walter, Je, Berger, Ct, Nobre, R, Roscioli, T, Buckley, Mf, Ziegler, Jb, Wong, M, Megarbane, A, Chouery, E, Lefranc, G, Hess, C, Tangye, S, Notarangelo, Luigi Daniele, and Bloch, D.
- Published
- 2012
24. A peptide derived from the Wiskott-Aldrich syndrome (WAS) protein-interacting protein (WIP) restores WAS protein level and actincytoskeleton reorganization in lymphocytes from patients with WAS mutations that disrupt WIP binding
- Author
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Massaad, Mj, Ramesh, N, Le Bras, S, Giliani, Silvia Clara, Notarangelo, Luigi Daniele, Al Herz, W, and Geha, Rs
- Published
- 2011
25. IL-21 is the primary common gamma chain-binding cytokine requiredfor human B-cell differentiation in vivo
- Author
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Recher, M, Berglund, Lj, Avery, Dt, Cowan, Mj, Gennery, Ar, Smart, J, Peake, J, Wong, M, Pai, Sy, Baxi, S, Walter, Je, Palendira, U, Tangye, Ga, Rice, M, Brothers, S, Al Herz, W, Oettgen, H, Eibel, H, Puck, Jm, Cattaneo, F, Ziegler, Jb, Giliani, Silvia Clara, Tangye, Sg, and Notarangelo, L. D.
- Published
- 2011
26. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency
- Author
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Al-Herz, W, Bousfiha, A, Casanova, J-L, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Franco, JL, Gaspar, HB, Holland, SM, Klein, C, Nonoyama, S, Ochs, HD, Oksenhendler, E, Picard, C, Puck, JM, Sullivan, K, Tang, MLK, Al-Herz, W, Bousfiha, A, Casanova, J-L, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Franco, JL, Gaspar, HB, Holland, SM, Klein, C, Nonoyama, S, Ochs, HD, Oksenhendler, E, Picard, C, Puck, JM, Sullivan, K, and Tang, MLK
- Abstract
We report the updated classification of primary immunodeficiencies (PIDs) compiled by the Expert Committee of the International Union of Immunological Societies. In comparison to the previous version, more than 30 new gene defects are reported in this updated version. In addition, we have added a table of acquired defects that are phenocopies of PIDs. For each disorder, the key clinical and laboratory features are provided. This classification is the most up-to-date catalog of all known PIDs and acts as a current reference of the knowledge of these conditions and is an important aid for the molecular diagnosis of patients with these rare diseases.
- Published
- 2014
27. Primary immunodefciency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Priary Immunodeficiency
- Author
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Al-Herz, W, Bousfiha, A, Casanova, J-L, Chapel, H, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Fischer, A, Luis Franco, J, Geha, RS, Hammarstrom, L, Nonoyama, S, Notarangelo, LD, Ochs, HD, Puck, JM, Roifman, CM, Seger, R, Tang, MLK, Al-Herz, W, Bousfiha, A, Casanova, J-L, Chapel, H, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Fischer, A, Luis Franco, J, Geha, RS, Hammarstrom, L, Nonoyama, S, Notarangelo, LD, Ochs, HD, Puck, JM, Roifman, CM, Seger, R, and Tang, MLK
- Abstract
We report the updated classification of primary immunodeficiency diseases, compiled by the ad hoc Expert Committee of the International Union of Immunological Societies. As compared to the previous edition, more than 15 novel disease entities have been added in the updated version. For each disorders, the key clinical and laboratory features are provided. This updated classification is meant to help in the diagnostic approach to patients with these diseases.
- Published
- 2011
28. Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency
- Author
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Walter, J E, Rucci, F, Patrizi, L, Recher, M, Regenass, S, Paganini, T, Keszei, M, Pessach, I, Lang, P A, Poliani, P L, Giliani, S, Al-Herz, W, Cowan, M J, Puck, J M, Bleesing, J, Niehues, T, Schuetz, C, Malech, H, DeRavin, S S, Facchetti, F, Gennery, A R, Andersson, E, Kamani, N R, Sekiguchi, J, Alenezi, H M, Chinen, J, Dbaibo, G, ElGhazali, G, Fontana, A, Pasic, S, Detre, C, Terhorst, C, Alt, F W, Notarangelo, L D, Walter, J E, Rucci, F, Patrizi, L, Recher, M, Regenass, S, Paganini, T, Keszei, M, Pessach, I, Lang, P A, Poliani, P L, Giliani, S, Al-Herz, W, Cowan, M J, Puck, J M, Bleesing, J, Niehues, T, Schuetz, C, Malech, H, DeRavin, S S, Facchetti, F, Gennery, A R, Andersson, E, Kamani, N R, Sekiguchi, J, Alenezi, H M, Chinen, J, Dbaibo, G, ElGhazali, G, Fontana, A, Pasic, S, Detre, C, Terhorst, C, Alt, F W, and Notarangelo, L D
- Abstract
The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro-B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP-keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4(+) T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell-activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations.
- Published
- 2010
29. A2.23 Impaired Natural Killer Cell Function in DOCK8 Deficiency
- Author
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Mizesko, MC, primary, Banerjee, PP, additional, Monaco-Shawver, L, additional, Mace, EM, additional, Bernal, W, additional, Sawalle-Belohradsky, J, additional, Belohradsky, B, additional, Heinz, V, additional, Freeman, AF, additional, Sullivan, KE, additional, Holland, SM, additional, Torgerson, TR, additional, Al-Herz, W, additional, Chou, J, additional, Hanson, IC, additional, Albert, MH, additional, Geha, RS, additional, Renner, ED, additional, and Orange, JS, additional
- Published
- 2013
- Full Text
- View/download PDF
30. Mortality Among Primary Immunodeficient Patients in Kuwait
- Author
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Al-Herz, W., primary
- Published
- 2010
- Full Text
- View/download PDF
31. A homozygous contiguous gene deletion in chromosome 16p13.3 leads to autosomal recessive osteopetrosis in a Jordanian patient.
- Author
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Pangrazio A, Frattini A, Valli R, Maserati E, Susani L, Vezzoni P, Villa A, Al-Herz W, Sobacchi C, Pangrazio, Alessandra, Frattini, Annalisa, Valli, Roberto, Maserati, Emanuela, Susani, Lucia, Vezzoni, Paolo, Villa, Anna, Al-Herz, Waleed, and Sobacchi, Cristina
- Subjects
CHROMOSOMES ,CYTOGENETICS ,DOCUMENTATION ,GENES ,MEMBRANE proteins ,GENETIC mutation ,NUCLEOTIDES ,OSTEOPETROSIS ,RESEARCH funding ,PHENOTYPES ,GENOTYPES - Abstract
Human malignant autosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder caused by reduced bone resorption by osteoclasts. Mutations in the CLCN7 gene are responsible not only for a substantial portion of ARO patients but also for other forms of osteopetrosis characterized by different severity and inheritance. The lack of a clear genotype/phenotype correlation makes genetic counseling a tricky issue for CLCN7-dependent osteopetrosis. Here, we characterize the first homozygous interstitial deletion in 16p13.3, detected by array comparative genomic hybridization in an ARO patient of Jordanian origin. The deletion involved other genes besides CLCN7, while the proband displayed a classic ARO phenotype; however, her early death did not allow more extensive clinical investigations. The identification of this novel genomic deletion involving a large part of the CLCN7 gene is of clinical relevance, especially in prenatal diagnosis, and suggests the possibility that this kind of mutation has been underestimated so far. These data highlight the need for alternative approaches to genetic analysis also in other ARO-causative genes. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
32. Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency
- Author
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Je, Walter, Lb, Rosen, Csomos K, Jm, Rosenberg, Mathew D, Keszei M, Ujhazi B, Chen K, Yn, Lee, Tirosh I, Dobbs K, Al-Herz W, Mj, Cowan, Puck J, and Ld, Notarangelo
33. Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency
- Author
-
Walter, J E, Rucci, F, Patrizi, L, Recher, M, Regenass, S, Paganini, T, Keszei, M, Pessach, I, Lang, P A, Poliani, P L, Giliani, S, Al-Herz, W, Cowan, M J, Puck, J M, Bleesing, J, Niehues, T, Schuetz, C, Malech, H, DeRavin, S S, Facchetti, F, Gennery, A R, Andersson, E, Kamani, N R, Sekiguchi, J, Alenezi, H M, Chinen, J, Dbaibo, G, ElGhazali, G, Fontana, A, Pasic, S, Detre, C, Terhorst, C, Alt, F W, and Notarangelo, L D
- Subjects
3. Good health
34. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency
- Author
-
Al-Herz W, Bousfiha A, Jl, Casanova, Chapel H, Me, Conley, Cunningham-Rundles C, Etzioni A, Fischer A, JOSE FRANCO, Rs, Geha, Hammarström L, Nonoyama S, and Ml, Tang
35. RANTES and eotaxin-1 in the gut of children with eosinophilic gastroenteropathy
- Author
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McGeady, S.J., Lateef, A., Barone, C., Justinich, C.J., and Al-Herz, W.
- Published
- 2003
- Full Text
- View/download PDF
36. The Prevalence and Distribution of Primary Immunodeficiency Disorders in Children in Kuwait.
- Author
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Al-Herz, W.
- Published
- 2008
- Full Text
- View/download PDF
37. Magnesium sulfate-induced nonallergic anaphylaxis.
- Author
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Al-Fares AA, Abdulmalek KA, and Al-Herz W
- Published
- 2007
- Full Text
- View/download PDF
38. Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity
- Author
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Ludmila Perelygina, Raeesa Faisthalab, Emily Abernathy, Min-hsin Chen, LiJuan Hao, Lionel Bercovitch, Diana K. Bayer, Lenora M. Noroski, Michael T. Lam, Maria Pia Cicalese, Waleed Al-Herz, Arti Nanda, Joud Hajjar, Koen Vanden Driessche, Shari Schroven, Julie Leysen, Misha Rosenbach, Philipp Peters, Johannes Raedler, Michael H. Albert, Roshini S. Abraham, Hemalatha G. Rangarjan, David Buchbinder, Lisa Kobrynski, Anne Pham-Huy, Julie Dhossche, Charlotte Cunningham Rundles, Anna K. Meyer, Amy Theos, T. Prescott Atkinson, Amy Musiek, Mehdi Adeli, Ute Derichs, Christoph Walz, Renate Krüger, Horst von Bernuth, Christoph Klein, Joseph Icenogle, Fabian Hauck, Kathleen E. Sullivan, Perelygina, L., Faisthalab, R., Abernathy, E., Chen, M. -H., Hao, L., Bercovitch, L., Bayer, D. K., Noroski, L. M., Lam, M. T., Cicalese, M. P., Al-Herz, W., Nanda, A., Hajjar, J., Vanden Driessche, K., Schroven, S., Leysen, J., Rosenbach, M., Peters, P., Raedler, J., Albert, M. H., Abraham, R. S., Rangarjan, H. G., Buchbinder, D., Kobrynski, L., Pham-Huy, A., Dhossche, J., Cunningham Rundles, C., Meyer, A. K., Theos, A., Atkinson, T. P., Musiek, A., Adeli, M., Derichs, U., Walz, C., Kruger, R., von Bernuth, H., Klein, C., Icenogle, J., Hauck, F., and Sullivan, K. E.
- Subjects
Male ,inborn errors of immunity ,Neutrophils ,Immunology ,skin lesion ,primary immunodeficiency ,Cohort Studies ,Th2 Cells ,neutrophils ,granulomatous inflammation ,granuloma treatments ,Humans ,Immunology and Allergy ,Antigens, Viral ,Rubella ,Aged ,Original Research ,Inflammation ,Granuloma ,Tumor Necrosis Factor-alpha ,Macrophages ,Genetic Diseases, Inborn ,Hematopoietic Stem Cell Transplantation ,Immunologic Deficiency Syndromes ,Receptors, Interleukin-1 ,RC581-607 ,Middle Aged ,Immunohistochemistry ,macrophages ,vaccine-derived rubella viruses ,Cytokines ,Female ,Human medicine ,Disease Susceptibility ,Immunologic diseases. Allergy ,Rubella virus - Abstract
Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.
- Published
- 2021
39. Failure of metabolic checkpoint control during late-stage granulopoiesis drives neutropenia in reticular dysgenesis.
- Author
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Wang W, Arreola M, Mathews T, DeVilbiss AW, Zhao Z, Martin-Sandoval M, Mohammed A, Benegiamo G, Awani A, Goeminne LJE, Dever DP, Nakauchi Y, Porteus MH, Pavel-Dinu M, Al Herz W, Auwerx J, Morrison SJ, and Weinacht KG
- Abstract
Cellular metabolism is highly dynamic during hematopoiesis, yet the regulatory networks that maintain metabolic homeostasis during differentiation are incompletely understood. Here, we have studied the grave immunodeficiency syndrome reticular dysgenesis caused by loss of mitochondrial adenylate kinase 2 (AK2) function. By coupling single-cell transcriptomics in reticular dysgenesis patient samples with a CRISPR model of this disorder in primary human hematopoietic stem cells, we found that the consequences of AK2 deficiency for the hematopoietic system are contingent on the effective engagement of metabolic checkpoints. In hematopoietic stem and progenitor cells, including early granulocyte precursors, AK2 deficiency reduced mechanistic target of rapamycin (mTOR) signaling and anabolic pathway activation. This conserved nutrient homeostasis and maintained cell survival and proliferation. In contrast, during late-stage granulopoiesis, metabolic checkpoints were ineffective, leading to a paradoxical upregulation of mTOR activity and energy-consuming anabolic pathways such as ribonucleoprotein synthesis in AK2-deficient cells. This caused nucleotide imbalance, including highly elevated AMP and IMP levels, the depletion of essential substrates such as NAD+ and aspartate, and ultimately resulted in proliferation arrest and demise of the granulocyte lineage. Our findings suggest that even severe metabolic defects can be tolerated with the help of metabolic checkpoints but that the failure of such checkpoints in differentiated cells results in a catastrophic loss of homeostasis., (Copyright © 2024 American Society of Hematology.)
- Published
- 2024
- Full Text
- View/download PDF
40. Germline mutations in a G protein identify signaling cross-talk in T cells.
- Author
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Ham H, Jing H, Lamborn IT, Kober MM, Koval A, Berchiche YA, Anderson DE, Druey KM, Mandl JN, Isidor B, Ferreira CR, Freeman AF, Ganesan S, Karsak M, Mustillo PJ, Teo J, Zolkipli-Cunningham Z, Chatron N, Lecoquierre F, Oler AJ, Schmid JP, Kuhns DB, Xu X, Hauck F, Al-Herz W, Wagner M, Terhal PA, Muurinen M, Barlogis V, Cruz P, Danielson J, Stewart H, Loid P, Rading S, Keren B, Pfundt R, Zarember KA, Vill K, Potocki L, Olivier KN, Lesca G, Faivre L, Wong M, Puel A, Chou J, Tusseau M, Moutsopoulos NM, Matthews HF, Simons C, Taft RJ, Soldatos A, Masle-Farquhar E, Pittaluga S, Brink R, Fink DL, Kong HH, Kabat J, Kim WS, Bierhals T, Meguro K, Hsu AP, Gu J, Stoddard J, Banos-Pinero B, Slack M, Trivellin G, Mazel B, Soomann M, Li S, Watts VJ, Stratakis CA, Rodriguez-Quevedo MF, Bruel AL, Lipsanen-Nyman M, Saultier P, Jain R, Lehalle D, Torres D, Sullivan KE, Barbarot S, Neu A, Duffourd Y, Similuk M, McWalter K, Blanc P, Bézieau S, Jin T, Geha RS, Casanova JL, Makitie OM, Kubisch C, Edery P, Christodoulou J, Germain RN, Goodnow CC, Sakmar TP, Billadeau DD, Küry S, Katanaev VL, Zhang Y, Lenardo MJ, and Su HC
- Subjects
- Humans, Cell Movement genetics, Cell Proliferation, Immunity genetics, MAP Kinase Signaling System, Phosphatidylinositol 3-Kinases metabolism, Phosphatidylinositol 3-Kinases genetics, Proto-Oncogene Proteins c-akt metabolism, ras Proteins metabolism, ras Proteins genetics, Signal Transduction, Pedigree, Germ-Line Mutation, GTP-Binding Protein alpha Subunit, Gi2 genetics, ras GTPase-Activating Proteins genetics, Receptors, Antigen, T-Cell metabolism, T-Lymphocytes immunology, T-Lymphocytes metabolism
- Abstract
Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G
αi2 , a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase-mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating Gαi2 mutations had clinical presentations that included impaired immunity. Mutant Gαi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant Gαi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)-activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-AKT S6 signaling to drive cellular growth and proliferation.- Published
- 2024
- Full Text
- View/download PDF
41. Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis.
- Author
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Chiang SCC, Covill LE, Tesi B, Campbell TM, Schlums H, Nejati-Zendegani J, Mördrup K, Wood S, Theorell J, Sekine T, Al-Herz W, Akar HH, Belen FB, Chan MY, Devecioglu O, Aksu T, Ifversen M, Malinowska I, Sabel M, Unal E, Unal S, Introne WJ, Krzewski K, Gilmour KC, Ehl S, Ljunggren HG, Nordenskjöld M, Horne A, Henter JI, Meeths M, and Bryceson YT
- Subjects
- Humans, Adolescent, Child, Adult, Female, K562 Cells, Male, Child, Preschool, Middle Aged, Infant, Young Adult, Aged, Sensitivity and Specificity, Prospective Studies, Receptors, Antigen, T-Cell metabolism, Receptors, Antigen, T-Cell genetics, Exocytosis, T-Lymphocytes, Cytotoxic immunology, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic immunology, Lymphohistiocytosis, Hemophagocytic genetics, Lymphohistiocytosis, Hemophagocytic pathology, Killer Cells, Natural immunology, Killer Cells, Natural metabolism
- Abstract
Abstract: Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder associated with autosomal recessive variants in genes required for perforin-mediated lymphocyte cytotoxicity. A rapid diagnosis is crucial for successful treatment. Although defective cytotoxic T lymphocyte (CTL) function causes pathogenesis, quantification of natural killer (NK)-cell exocytosis triggered by K562 target cells currently represents a standard diagnostic procedure for primary HLH. We have prospectively evaluated different lymphocyte exocytosis assays in 213 patients referred for evaluation for suspected HLH and related hyperinflammatory syndromes. A total of 138 patients received a molecular diagnosis consistent with primary HLH. Assessment of Fc receptor-triggered NK-cell and T-cell receptor (TCR)-triggered CTL exocytosis displayed higher sensitivity and improved specificity for the diagnosis of primary HLH than routine K562 cell-based assays, with these assays combined providing a sensitivity of 100% and specificity of 98.3%. By comparison, NK-cell exocytosis after K562 target cell stimulation displayed a higher interindividual variability, in part explained by differences in NK-cell differentiation or large functional reductions after shipment. We thus recommend combined analysis of TCR-triggered CTL and Fc receptor-triggered NK-cell exocytosis for the diagnosis of patients with suspected familial HLH or atypical manifestations of congenital defects in lymphocyte exocytosis., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)
- Published
- 2024
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42. Regulatory T-cell dysfunction and cutaneous exposure to Staphylococcus aureus underlie eczema in DOCK8 deficiency.
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Wilkie H, Das M, Pelovitz T, Bainter W, Woods B, Alasharee M, Sobh A, Baris S, Eltan SB, Al-Herz W, Barbouche MR, Ben-Mustapha I, Ben-Ali M, Sallam MTH, Awad A, Lotfy S, El Marsafy A, Ezzelarab M, Farrar M, Schmidt BAR, NandyMazumdar M, Guttman-Yassky E, Sheets A, Vidic KM, Murphy G, Schlievert PM, Chou J, Leyva-Castillo JM, Janssen E, Timilshina M, and Geha RS
- Subjects
- Animals, Humans, Mice, Female, Male, Mice, Inbred C57BL, Dermatitis, Atopic immunology, T-Lymphocytes, Regulatory immunology, Guanine Nucleotide Exchange Factors deficiency, Guanine Nucleotide Exchange Factors genetics, Guanine Nucleotide Exchange Factors immunology, Eczema immunology, Staphylococcus aureus immunology, Skin immunology, Skin pathology, Mice, Knockout
- Abstract
Background: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD)., Objective: We sought to understand the mechanisms of eczema in DOCK8 deficiency., Methods: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression. Skin barrier function was measured by transepidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous sensitization with ovalbumin (OVA) or cutaneous application of Staphylococcus aureus., Results: Skin lesions of DOCK8-deficient patients exhibited type 2 inflammation, and the patients' skin was colonized by Saureus, as in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8
-/- mice exhibited reduced numbers of cutaneous T regulatory (Treg) cells and a normal skin barrier. Dock8-/- and mice with an inducible Dock8 deletion in Treg cells exhibited increased allergic skin inflammation after epicutaneous sensitization with OVA. DOCK8 was shown to be important for Treg cell stability at sites of allergic inflammation and for the generation, survival, and suppressive activity of inducible Treg cells. Adoptive transfer of wild-type, but not DOCK8-deficient, OVA-specific, inducible Treg cells suppressed allergic inflammation in OVA-sensitized skin of Dock8-/- mice. These mice developed severe allergic skin inflammation and elevated serum IgE levels after topical exposure to Saureus. Both were attenuated after adoptive transfer of WT but not DOCK8-deficient Treg cells., Conclusion: Treg cell dysfunction increases susceptibility to allergic skin inflammation in DOCK8 deficiency and synergizes with cutaneous exposure to Saureus to drive eczema in DOCK8 deficiency., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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43. A case report of a patient with recurrent and severe infections highlighting the importance of considering inborn errors of immunity.
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Altammar F, Alshamali M, Alqunaee M, Alali AJ, Elshafie RM, and Al-Herz W
- Abstract
Inborn errors of immunity (IEI) can often be misdiagnosed early in life due to their heterogenous clinical presentations. Interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency is one of the rare innate immunodeficiency disorders. We present the case of a patient who presented at the age of 15 days with meningitis and septic shock that responded to antibiotics. She was admitted again at the age of 45 days with pseudomonas aeruginosa bacteremia that was associated with increased inflammatory markers. Her third admission was at the age of 2.5 months due to left sided peri-orbital cellulitis that was again associated with elevated inflammatory markers. At 3.5 months, she experienced left orbital cellulitis, which was complicated by extensive sinus involvement, erosion, and abscess formation in the pterygopalatine fossa. Her condition progressed to septic shock and required multiple antibiotics and surgical interventions for drainage and control of the infection source. Both abscess and blood culture were positive for pseudomonas aeruginosa . An IEI was suspected but basic immunology testing was normal. Whole Exome Sequencing was performed and a novel mutation in IRAK4 was detected. In conclusion, we highlight the importance of raising awareness among pediatricians about the potentially lethal IEI and the need to consult specialists when these diseases are suspected. Among them is IRAK-4 deficiency which can be diagnosed by sophisticated functional assays and/or genetic testing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Altammar, Alshamali, Alqunaee, Alali, Elshafie and Al-Herz.)
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- 2024
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44. Epidemiology of combined immunodeficiencies affecting cellular and humoral immunity- a multicentric retrospective cohort study from the Arabian Peninsula.
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Al-Herz W, Ziyab AH, Adeli M, Al Farsi T, Al-Hammadi S, Al Kuwaiti AA, Al-Nesf M, Al Sukaiti N, Al-Tamemi S, and Shendi H
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- Infant, Newborn, Humans, Retrospective Studies, Immunity, Humoral, Neonatal Screening, Hematopoietic Stem Cell Transplantation, Primary Immunodeficiency Diseases
- Abstract
Aims: To understand the characteristics of combined immunodeficiency disorders that affect cellular and humoral immunity (CID) in the Arabian Peninsula., Methods: Retrospective study of 236 patients with CID from the region were enrolled from 2004 to 2022., Results: 236 patients were included with a majority being profound CID. Among patients with a family history of CID, the ages at onset and diagnosis, and the delay in diagnosis were lower compared to those with no family history of CID, but this did not affect time to transplant. HSCT was performed for 51.27% of the patients with median time from diagnosis to HSCT of 6.36 months. On multivariate analysis, patients who underwent early transplant had increased odds of having CD3 count ≤1000 cell/μl, diagnosed by screening or erythroderma., Conclusion: There is a delay in diagnosis and treatment of CID in our region. Establishing newborn screening programs and HSCT units in our region are the urgent need., Competing Interests: Declaration of Competing Interest none., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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45. Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN).
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Park SH, Hong SH, Kim K, Lee SW, Yon DK, Jung SJ, Abdeen Z, Ghayda RA, Ahmed MLCB, Serouri AA, Al-Herz W, Al-Shamsi HO, Ali S, Ali K, Baatarkhuu O, Nielsen HB, Bernini-Carri E, Bondarenko A, Cassell A, Cham A, Chua MLK, Dadabhai S, Darre T, Davtyan H, Dragioti E, East B, Edwards RJ, Ferioli M, Georgiev T, Ghandour LA, Harapan H, Hsueh PR, Mallah SI, Ikram A, Inoue S, Jacob L, Janković SM, Jayarajah U, Jesenak M, Kakodkar P, Kapata N, Kebede Y, Khader Y, Kifle M, Koh D, Maleš VK, Kotfis K, Koyanagi A, Kretchy JP, Lakoh S, Lee J, Lee JY, Mendonça MDLL, Ling L, Llibre-Guerra J, Machida M, Makurumidze R, Memish ZA, Mendoza I, Moiseev S, Nadasdy T, Nahshon C, Ñamendys-Silva SA, Yongsi BN, Nicolasora AD, Nugmanova Z, Oh H, Oksanen A, Owopetu O, Ozguler ZO, Parperis K, Perez GE, Pongpirul K, Rademaker M, Radojevic N, Roca A, Rodriguez-Morales AJ, Roshi E, Saeed KMI, Sah R, Sakakushev B, Sallam DE, Sathian B, Schober P, Ali PSS, Simonović Z, Singhal T, Skhvitaridze N, Solmi M, Subbaram K, Tizaoui K, Tlhakanelo JT, Torales J, Torres-Roman JS, Tsartsalis D, Tsolmon J, Vieira DN, Rosa SGV, Wanghi G, Wollina U, Xu RH, Yang L, Zia K, Zildzic M, Il Shin J, and Smith L
- Subjects
- Humans, SARS-CoV-2, Incidence, Cross-Sectional Studies, Quarantine, COVID-19 epidemiology
- Abstract
The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19., (© 2022 Wiley Periodicals LLC.)
- Published
- 2023
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46. The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity.
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Baris S, Abolhassani H, Massaad MJ, Al-Nesf M, Chavoshzadeh Z, Keles S, Reisli I, Tahiat A, Shendi HM, Elaziz DA, Belaid B, Al Dhaheri F, Haskologlu S, Dogu F, Ben-Mustapha I, Sobh A, Galal N, Meshaal S, Elhawary R, El-Marsafy A, Alroqi FJ, Al-Saud B, Al-Ahmad M, Al Farsi T, Al Sukaiti N, Al-Tamemi S, Mehawej C, Dbaibo G, ElGhazali G, Kilic SS, Genel F, Kiykim A, Musabak U, Artac H, Guner SN, Boukari R, Djidjik R, Kechout N, Cagdas D, El-Sayed ZA, Karakoc-Aydiner E, Alzyoud R, Barbouche MR, Adeli M, Wakim RH, Reda SM, Ikinciogullari A, Ozen A, Bousfiha A, Al-Mousa H, Rezaei N, Al-Herz W, and Geha RS
- Subjects
- Adult, Child, Humans, Africa, Northern epidemiology, Middle East epidemiology, Phenotype, Registries, Consanguinity
- Abstract
Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders. This area also exhibits more severe disease phenotypes compared with other regions, probably due to the delay in diagnosis. The MENA-IEI registry network has designed protocols and guidelines for the diagnosis and treatment of IEI, taking into consideration the variable regional expertise and resources. These guidelines are primarily meant to improve the care of patients within the region, but can also be followed in other regions with similar patient populations., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. All rights reserved.)
- Published
- 2023
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47. Consensus on diagnosis and management of Hereditary Angioedema in the Middle East: A Delphi initiative.
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Maurer M, Abuzakouk M, Al-Ahmad M, Al-Herz W, Alrayes H, Al-Tamemi S, Arnaout R, Binghadeer H, Gutta R, Irani C, Mobayed H, Nasr I, Shendi H, and Zaitoun F
- Abstract
Background: Hereditary angioedema (HAE), a potentially life-threatening genetic disorder due to C1 inhibitor deficiency in most cases, is characterized by sudden and/or recurrent attacks of angioedema (subcutaneous/submucosal swellings). The global World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) International guideline for HAE management is comprehensive, but the implementation of this guideline may require regional adaptation considering the diversity in disease awareness, type of medical care systems, and access to diagnostics and treatment. The aim of this Delphi initiative was to build on the global guideline and provide regional adaptation to address the concerns and specific needs in the Middle East., Methods: The Consensus panel comprised 13 experts from the Middle East (3 from the United Arab Emirates, 3 from Saudi Arabia, 2 from Lebanon, 2 from Kuwait, 2 from Oman and 1 from Qatar) who have more than 2 decades of experience in allergy and immunology and are actively involved in managing HAE patients. The process that was carried out to reach the consensus recommendation included: 1.) A systematic literature review for articles related to HAE management using Ovid MEDLINE. 2.) The development of a questionnaire by an internationally acclaimed expert, with 10 questions specific to HAE management in the Middle East. 3.) Experts received the questionnaire via email individually and their answers were recorded (email/interview). 4.) A virtual consensus meeting was organized to discuss the questionnaire, make amends if needed, vote, and achieve consensus., Results: The questionnaire comprised 10 questions, each with 2 or more statements/recommendations on which the regional experts voted. A consensus was reached based on a 70% agreement between the participants. The key highlights include: 1) HAE experts in the Middle East emphasized the importance of a positive family history for arriving at a diagnosis of HAE. 2) The number of episodes per month or per 6-month period and severity should be used, together with other markers, to determine the need for prophylaxis. 3) Disease status should be monitored by periodic visits and the use of patient-reported outcome measures such as the angioedema activity score and the angioedema control test. 4) Attenuated androgens and tranexamic acid may be considered for long-term prophylaxis, if lanadelumab, C1-Inhibitor or berotralstat are not available., Conclusion: This consensus recommendation may help to educate healthcare practitioners in the Middle East and unify their approach to the diagnosis and management of HAE., (© 2022 The Authors.)
- Published
- 2022
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48. Predictors of early death risk among untransplanted patients with combined immunodeficiencies affecting cellular and humoral immunity: A multicenter report.
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Al-Herz W, Ziyab AH, Adeli M, Al Farsi T, Al-Hammadi S, Al Kuwaiti AA, Al-Nesf M, Al Sukaiti N, Al-Tamemi S, and Shendi H
- Subjects
- Humans, Infant, Immunity, Humoral, Retrospective Studies, Hepatomegaly etiology, Primary Immunodeficiency Diseases etiology, Sepsis etiology, Candidiasis etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Background: There is an increased demand for hematopoietic stem cell transplant (HSCT) to treat various diseases including combined immunodeficiencies (CID), with limited worldwide availability. Variables affecting the decision regarding CID patients' prioritization for HSCT are not known. We aimed to determine general, clinical, and immunologic factors associated with the higher risk of early death (≤6 months after diagnosis) in untransplanted CID patients., Methods: Data collection was done retrospectively from five centers and included general patients' information, and clinical and laboratory variables. Inclusion criteria were untransplanted patients who are either dead or alive with a follow-up period ≥6 months after diagnosis., Results: Two hundred and thirty-six CID patients were reported by participating centers, of whom 111 were included in the study with a cumulative follow-up period of 278.6 years. Seventy-two patients died with the median age of death of 10.5 months. 35.1% of the patients succumbed within 6 months after the diagnosis. Having a history of Candida infections, sepsis or hepatomegaly was associated with an increased risk of early death. None of the other general or clinical variables was associated with such risk. Bivariate analysis of lymphocyte subsets showed that patients with the following counts: CD3
+ < 100, CD4+ < 200, CD8+ < 50, or CD16+ CD56+ <200 cells/μl had increased risk of early death. In adjusted analysis, increased risk of early death was observed among patients with CD3+ count <100 cells/μl., Conclusion: Combined immunodeficiencies patients with a history of Candida infections, sepsis, hepatomegaly, or severe T-lymphopenia should be given priority for HSCT to avoid early death., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)- Published
- 2022
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49. BCG Vaccine-associated Complications in a Large Cohort of Children With Combined Immunodeficiencies Affecting Cellular and Humoral Immunity.
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Al-Herz W, Husain EH, Adeli M, Al Farsi T, Al-Hammadi S, Al Kuwaiti AA, Al-Nesf M, Al Sukaiti N, Al-Tamemi S, and Shendi H
- Subjects
- Child, Humans, Infant, Infant, Newborn, Immunity, Humoral, Immunoglobulins, Retrospective Studies, Vaccination adverse effects, BCG Vaccine adverse effects, Mycobacterium bovis, Primary Immunodeficiency Diseases complications
- Abstract
Aims: To present the details of Bacillus Calmette-Guérin (BCG)-vaccine associated complications (VACs) in combined immunodeficiencies (CID) patients., Methods: Five centers participated in this retrospective study and completed a data form, which included general patients' information, clinical and laboratory data., Results: Among 236 CID patients, 127 were BCG vaccinated. 41.9% of patients with family history of CID and 17.1% who were diagnosed by screening were BCG vaccinated. Twenty-three patients (18.1%) developed BCG-VACs. The median age of VACs was 6 months and the median time from vaccination to complications was 6 months. The highest rate of BCG-VACs was recorded in patients receiving the Russian BCG strain compared to the Tokyo and Danish strains. Univariate analysis of T-lymphocyte subsets showed increased odds of BCG complications in patients with CD3+, CD4+, and CD8+ counts of ≤250 cells/µL. Only CD8 + count ≤250 cells/µL had increased such odds on multivariate analysis. VACs were disseminated in 13 and localized in 10 patients. Localized complication occurred earlier after vaccination (median: 4 months) compared with disseminated ones (median: 7 months). There were no significant associations between sex, administered vaccine strain, serum immunoglobulins levels, lymphocyte subsets counts, and the chance of having either localized or disseminated BCG-related complications., Coclusions: Although contraindicated, many patients with CID continue to be vaccinated with BCG. Low CD8 + count is a risk factor for BCG-related complications and localized complications occurred earlier than disseminated ones. Considerations should be undertaken by health care authorities especially in countries with high incidence of CID to implement newborn screening, delay the time of BCG vaccine administration beyond 6 months of age and to use the relatively safer strains like the Danish and Tokyo ones., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
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50. Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry.
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Jamee M, Azizi G, Baris S, Karakoc-Aydiner E, Ozen A, Kiliç SŞ, Kose H, Chavoshzadeh Z, Mahdaviani SA, Momen T, Shamsian BS, Fallahi M, Sharafian S, Gülez N, Aygun A, Karaca NE, Kutukculer N, Al Sukait N, Al Farsi T, Al-Tamemi S, Khalifa N, Shereen R, El-Ghoneimy D, El-Owaidy R, Radwan N, Alzyoud R, Barbouche MR, Ben-Mustapha I, Mekki N, Rais A, Boukari R, Belbouab R, Djenouhat K, Tahiat A, Touri S, Elghazali G, Al-Hammadi S, Shendi HM, Alkuwaiti A, Belaid B, Djidjik R, Artac H, Adeli M, Sobh A, Elnagdy MH, Bahgat SA, Nasrullayeva G, Chou J, Rezaei N, Al-Herz W, Geha RS, and Abolhassani H
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adolescent, Child, Child, Preschool, Egypt, Female, Humans, Male, Registries, Retrospective Studies, Tunisia, Turkey, Vesicular Transport Proteins genetics, rab27 GTP-Binding Proteins genetics, Primary Immunodeficiency Diseases genetics
- Abstract
Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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