13 results on '"Jahnavi Aluri"'
Search Results
2. A Case of Severe Combined Immunodeficiency Missed by Newborn Screening
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Jeffrey J. Bednarski, Maleewan Kitcharoensakkul, Megan A. Cooper, Ashley Steed, Ibrahim Elsharkawi, Anil Kumar Swayampakula, Christopher D. Putnam, and Jahnavi Aluri
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Male ,Severe combined immunodeficiency ,medicine.medical_specialty ,Newborn screening ,Pediatrics ,business.industry ,Immunology ,MEDLINE ,Infant ,medicine.disease ,Newborn ,Letter to Editor ,Medical microbiology ,Neonatal Screening ,medicine ,Immunology and Allergy ,Humans ,Severe Combined Immunodeficiency ,business - Published
- 2021
3. The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India
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Amruta Dhawale, Pallavi Gaikwad, Ramya Uppuluri, Snehal Shabrish, Swati Kanakia, Meena Sivasankaran, Ambreen Pandrowala, Dharani Jayaraman, Pranoti Kini, Abhilasha Sampagar, Deenadayalan Munirathnam, Sneha Sawant-Desai, Mukesh Desai, Aparna Dalvi, Shweta Shinde, Brijesh Arora, Pandiarajan Vignesh, Aaqib Zaffar Banday, Madhura Kelkar, Meenakshi Girish, Manisha Madkaikar, Jahnavi Aluri, Santanu Sen, Amit Rawat, Gouri Hule, Narendra K Chaudhary, Ramprasad Vedam, R Yadav, Nayana Nambiar, Umair Ahmed Bargir, Revathi Raj, Vijaya Gowri, Farah Jijina, Priyanka Setia, Neha Jodhawat, Manasi Kulkarni, M. R. Lokeshwar, Abhijit Chaudhary, S. Chandrakla, Priyanka Kambli, Ratna Sharma, Nitin Shah, Prasad Taur, Maya Gupta, Ujjal Poddar, and Amita Aggarwal
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Male ,lcsh:Immunologic diseases. Allergy ,Immunology ,India ,medicine.disease_cause ,Lymphohistiocytosis, Hemophagocytic ,familial hemophagocytic lymphohistocytosis ,T-Lymphocyte Subsets ,Databases, Genetic ,medicine ,Humans ,Immunology and Allergy ,Genetic Predisposition to Disease ,UNC13D ,HLH-targeted therapy ,Child ,flow cytomertry ,Alleles ,perforin ,Original Research ,degranulation ,Hemophagocytic lymphohistiocytosis ,biology ,Genetic heterogeneity ,business.industry ,Computational Biology ,Disease Management ,Infant ,Familial Hemophagocytic Lymphohistiocytosis ,Immune dysregulation ,medicine.disease ,Combined Modality Therapy ,Phenotype ,Treatment Outcome ,Perforin ,STX11 ,Child, Preschool ,NGS ,Mutation ,biology.protein ,Female ,Cytokine secretion ,Disease Susceptibility ,lcsh:RC581-607 ,business ,Biomarkers - Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified.
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- 2021
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4. Prenatal Diagnosis for Primary Immunodeficiency Disorders—An Overview of the Indian Scenario
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Jahnavi Aluri, R Yadav, Suresh Seshadri, Prerna Jhawar, Umair Ahmed Bargir, Snehal Shabrish, Karthik Bharadwaj Tallapaka, Beena Guhan, Malathi Prasad, Manisha Madkaikar, Mukesh Desai, Sivasankar Malaischamy, B. Suresh, Manasi Kulkarni, Sagar Bhattad, Geeta Madathil Govindaraj, Revathi Raj, Vasundhara Tamhankar, Aparna Dalvi, Shilpa Mithbawkar, Jayarekha Raja, Ramya Uppuluri, Vandana Bansal, Gouri Hule, Harsha Prasada Lashkari, Sujatha Jagadeesh, Priyanka Ghosh, Priya Kadam, Parag M Tamhankar, Adinarayan Makam, Priyanka Kambli, Prasad Taur, Maya Gupta, and Shweta Mahalingam
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0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,chorionic villus sampling ,Primary Immunodeficiency Diseases ,Genetic counseling ,Immunology ,India ,Chorionic villus sampling ,Prenatal diagnosis ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Humans ,Immunology and Allergy ,Genetic Testing ,Index case ,reproductive and urinary physiology ,variants of unknown significance ,Original Research ,030219 obstetrics & reproductive medicine ,prenatal diagnosis ,medicine.diagnostic_test ,business.industry ,Obstetrics ,flow cytometry ,Genetic Diseases, Inborn ,medicine.disease ,maternal contamination ,Indian scenario ,030104 developmental biology ,Mutation ,Amniocentesis ,Primary immunodeficiency ,Female ,business ,lcsh:RC581-607 ,cordocentesis - Abstract
Prenatal Diagnosis (PND) forms an important part of primary preventive management for families having a child affected with primary immunodeficiency. Although individually sparse, collectively this group of genetic disorders represents a significant burden of disease. This paper discusses the prenatal services available for affected families at various centers across the country and the challenges and ethical considerations associated with genetic counseling. Mutation detection in the index case and analysis of chorionic villous sampling or amniocentesis remain the preferred procedures for PND and phenotypic analysis of cordocentesis sample is reserved for families with well-characterized index case seeking PND in the latter part of the second trimester of pregnancy. A total of 112 families were provided PND services in the last decade and the presence of an affected fetus was confirmed in 32 families. Post-test genetic counseling enabled the affected families to make an informed decision about the current pregnancy.
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- 2020
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5. Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India
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Neha Jodhawat, Manasi Kulkarni, Snehal Shabrish, Prasad Taur, Umair Ahmed Bargir, Mukesh Desai, Maya Gupta, Gouri Hule, Priyanka Kambli, Jahnavi Aluri, Manisha Madkaikar, Aparna Dalvi, Priyanka Setia, and R Yadav
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0301 basic medicine ,Male ,Pediatrics ,medicine.medical_specialty ,Tuberculosis ,Immunology ,India ,Granulomatous Disease, Chronic ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Family history ,Tuberculosis, Pulmonary ,Immunodeficiency ,business.industry ,Incidence (epidemiology) ,Vaccination ,Infant ,General Medicine ,Mycobacterium tuberculosis ,medicine.disease ,030104 developmental biology ,Treatment Outcome ,Cohort ,Primary immunodeficiency ,BCG Vaccine ,Female ,Severe Combined Immunodeficiency ,business ,BCG vaccine ,030215 immunology - Abstract
World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR- National Institute of Immunohematology (ICMR-NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN-γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.
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- 2020
6. Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function
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Marina Cella, Mary C. Dinauer, Elaine Kulm, Michelle A. Ritter, Jahnavi Aluri, Alicia Bach, Elise M. Rizzi, Christina Bemrich-Stolz, Maleewan Kitcharoensakkul, Magdalena Walkiewicz, Jack J. Bleesing, Yi Shan Lee, James A. Connelly, Amy M. Scurlock, Laura G. Schuettpelz, Marwan Shinawi, Shirley M. Abraham, Saara Kaviany, V. Koneti Rao, Jonathan D. Powell, Jeffrey J. Bednarski, Peggy L. Kendall, Luana Chiquetto Paracatu, Raphaela Goldbach-Mansky, Christopher D. Putnam, Michael T. Harmon, Adriana Almeida de Jesus, Scott W. Canna, Stacie M. Jones, Morgan Similuk, Matthew M. Demczko, Nermina Saucier, Suk See De Ravin, Michael Joyce, Molly P. Keppel, and Megan A. Cooper
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Adult ,Male ,Immunobiology and Immunotherapy ,Adolescent ,Pancytopenia ,medicine.medical_treatment ,T-Lymphocytes ,Immunology ,Neutropenia ,Lymphocyte Activation ,Biochemistry ,Young Adult ,Immune system ,Immunity ,medicine ,Humans ,Child ,Immunodeficiency ,Inflammation ,B-Lymphocytes ,business.industry ,Mosaicism ,Bone marrow failure ,Immunologic Deficiency Syndromes ,Infant ,Cell Differentiation ,Cell Biology ,Hematology ,Bone Marrow Failure Disorders ,medicine.disease ,Prognosis ,Pedigree ,Transplantation ,Haematopoiesis ,Cytokine ,Toll-Like Receptor 8 ,Child, Preschool ,Gain of Function Mutation ,Cytokines ,Female ,business ,Follow-Up Studies - Abstract
Inborn errors of immunity (IEI) are a genetically heterogeneous group of disorders with a broad clinical spectrum. Identification of molecular and functional bases of these disorders is important for diagnosis, treatment, and an understanding of the human immune response. We identified 6 unrelated males with neutropenia, infections, lymphoproliferation, humoral immune defects, and in some cases bone marrow failure associated with 3 different variants in the X-linked gene TLR8, encoding the endosomal Toll-like receptor 8 (TLR8). Interestingly, 5 patients had somatic variants in TLR8 with
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- 2020
7. Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India
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Snehal Shabrish, Manisha Madkaikar, Uma P. Nalavade, Jahnavi Aluri, Mukesh Desai, Prasad Taur, Jagadish M. Deshpande, Maya Gupta, Aparna Dalvi, Deepa Sharma, Manasi Kulkarni, and Madhu Chhanda Mohanty
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Male ,0301 basic medicine ,Epidemiology ,viruses ,VDPV ,OPV ,lcsh:Medicine ,Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India ,medicine.disease_cause ,Feces ,0302 clinical medicine ,030212 general & internal medicine ,Child ,poliovirus ,enterovirus ,Poliovirus ,virus diseases ,Virus Shedding ,Poliomyelitis ,Infectious Diseases ,Child, Preschool ,Female ,Risk ,Microbiology (medical) ,oral polio vaccine ,India ,vaccine-derived polioviruses ,complex mixtures ,lcsh:Infectious and parasitic diseases ,Excretion ,03 medical and health sciences ,children ,Poliomyelitis eradication ,Enterovirus Infections ,medicine ,Humans ,primary immunodeficiency disorder ,lcsh:RC109-216 ,Severe combined immunodeficiency ,business.industry ,Research ,lcsh:R ,Immunologic Deficiency Syndromes ,Infant ,medicine.disease ,Virology ,Mumbai ,Enterovirus C, Human ,030104 developmental biology ,Poliovirus Vaccine, Oral ,Primary immunodeficiency ,Enterovirus ,business - Abstract
Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014-April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped.
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- 2017
8. Natural Clearance of Prolonged VDPV Infection in a Child With Primary Immunodeficiency Disorder
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Prasad Taur, Maya Gupta, Jagadish M. Deshpande, Aparna Dalvi, Mukesh Desai, Swapnil Yashwant Varose, Uma P. Nalavade, Deepa Kailash Sharma, Madhu Chhanda Mohanty, Jahnavi Aluri, Manisha Madkaikar, Sneha Vijay Rane, and Snehal Shabarish
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0301 basic medicine ,Serotype ,lcsh:Immunologic diseases. Allergy ,oral polio vaccine ,inflammatory cytokines ,Immunology ,Case Report ,medicine.disease_cause ,vaccine-derived polioviruses ,severe combined immune-deficiency ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cytotoxic T cell ,Medicine ,Immunology and Allergy ,primary immunodeficiency disorder ,Immunodeficiency ,Severe combined immunodeficiency ,business.industry ,Poliovirus ,medicine.disease ,030104 developmental biology ,Primary immunodeficiency ,leaky SCID ,business ,lcsh:RC581-607 ,CD8 ,030215 immunology - Abstract
The emergence of immunodeficiency-associated vaccine-derived polioviruses (iVDPV) from children with primary immunodeficiency disorders poses a threat to the eradication program. Herein, we report a patient with severe combined immunodeficiency (SCID), identified as a prolonged serotype 3 iVDPV (iVDPV3) excreter with 13 VDPV3 isolates and a maximum of 10.33% nucleotide divergence, who abruptly cleared infection after a period of 2 years. Occurrence of an episode of norovirus diarrhea associated with increased activated oligoclonal cytotoxic T cells, inverse CD4:CD8 ratio, significantly elevated pro-inflammatory cytokines, and subsequent clearance of the poliovirus suggests a possible link between inflammatory diarrheal illness and clearance of iVDPV. Our findings suggest that in the absence of B cells and sufficiently activated T/NK cells, macrophages and other T cells may produce auto-inflammatory conditions by TLR/RLR ligands expressed by previous/ongoing bacterial or viral infections to clear VDPV infection. The study highlights the need to screen all the patients with combined immunodeficiency for poliovirus excretion and intermittent follow-up of their immune parameters if found positive, in order to manage the risk of iVDPV excretion in the polio eradication endgame strategy.
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- 2019
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9. Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India
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Julie E. Niemela, Vidya Krishna, Jennifer Stoddard, Jahnavi Aluri, Sergio D. Rosenzweig, Manasi Kulkarni, Manisha Madkaikar, Geeta Madathil Govindaraj, Umair Ahmed Bargir, Amita Aggarwal, Harsha Prasada Lashkari, Aparna Dalvi, Mukesh Desai, Manas Kalra, Nitin Shah, Maya Gupta, Antony Terance, Vasundhara Tamankar, and Snehal Mhatre
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Male ,0301 basic medicine ,Lymphocyte ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Gastroenterology ,0302 clinical medicine ,Immunology and Allergy ,Medicine ,Age of Onset ,TREC ,sanger sequencing ,Original Research ,Combined Modality Therapy ,medicine.anatomical_structure ,Child, Preschool ,targeted next generation sequencing ,Cohort ,Failure to thrive ,Female ,Disease Susceptibility ,Symptom Assessment ,medicine.symptom ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,Immunology ,ZAP70 deficiency ,CD4-CD8 Ratio ,India ,03 medical and health sciences ,Internal medicine ,Humans ,Reticular dysgenesis ,Lymphocyte Count ,Severe combined immunodeficiency ,AIDS-Related Opportunistic Infections ,business.industry ,Gene Expression Profiling ,flow cytometry ,PID ,Infant, Newborn ,Genetic Variation ,Infant ,medicine.disease ,030104 developmental biology ,Primary immunodeficiency ,Severe Combined Immunodeficiency ,lcsh:RC581-607 ,business ,Biomarkers ,030215 immunology - Abstract
Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL
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- 2019
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10. Guidelines for Screening, Early Diagnosis and Management of Severe Combined Immunodeficiency (SCID) in India
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Jahnavi Aluri, Manisha Madkaikar, and Sudhir Gupta
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0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,India ,03 medical and health sciences ,Neonatal Screening ,0302 clinical medicine ,medicine ,Humans ,Newborn screening ,Severe combined immunodeficiency ,T-cell receptor excision circles ,business.industry ,Infant, Newborn ,Disease Management ,medicine.disease ,Transplantation ,Early Diagnosis ,030104 developmental biology ,medicine.anatomical_structure ,Cord blood ,Practice Guidelines as Topic ,Pediatrics, Perinatology and Child Health ,Immunology ,Primary immunodeficiency ,Severe Combined Immunodeficiency ,Bone marrow ,business ,BCG vaccine ,030215 immunology - Abstract
Severe combined immunodeficiency (SCID) is one of the most severe and fatal forms of inherited primary immunodeficiency. Early diagnosis of SCID improves the outcome of life before and after hematopoietic stem cell transplant (HSCT). SCID fulfills the internationally-established criteria for a condition to be screened for at birth. T cell receptor excision circle (TREC) assay is commonly used in western countries as part of newborn blood spot screening (NBS) program as the assay has high sensitivity and specificity to identify SCID infants, allowing early intervention and curative bone marrow (BM) transplantation. In India, the blood spot based screening programs are yet to mature into a full-fledged national program. Moreover, TREC assay, a PCR based test, is not widely available and may cost USD 5-7 per test; thus limiting its applicability for screening newborns in Indian scenario. Most of the SCID patients have lymphopenia at birth and routine evaluation for absolute lymphocyte count (ALC) on cord blood samples can help in pre-symptomatic detection and early intervention for neonates with SCID. Although ALC count lacks the sensitivity and specificity of TREC assay; its lower cost and widespread availability makes it an attractive option for identifying newborns with lymphopenia during the post-partum hospital stay. BCG vaccine and other live attenuated vaccines (e.g., oral polio vaccine) should be withheld in lymphopenic infants until SCID is excluded by clinical and/or immunological work-up. A diagnosis of SCID warrants immediate care to prevent and treat infections and wherever feasible, early stem cell transplantation for disease free survival.
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- 2016
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11. Lymphopenia and Severe Combined Immunodeficiency (SCID) - Think Before You Ink
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Jahnavi Aluri, Manisha Madkaikar, Mukesh Desai, Manasi Kulkarni, Aparna Dalvi, Nitin Shah, Maya Gupta, and Snehal Mhatre
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Male ,Lymphocyte ,T cell ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,030225 pediatrics ,Lymphopenia ,T cell immunity ,medicine ,T-cell lymphopenia ,Humans ,Lymphocyte Count ,Severe combined immunodeficiency ,T-cell receptor excision circles ,business.industry ,Infant ,medicine.disease ,Immunity, Humoral ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Immunology ,Primary immunodeficiency ,Female ,Severe Combined Immunodeficiency ,business ,030217 neurology & neurosurgery - Abstract
Severe combined immunodeficiency (SCID) represents one of the most severe forms of Primary immunodeficiency (PID) disorders, characterized by T cell lymphopenia (TCL) and lack of cellular and humoral immune responses. However, not all patients with low T cell lymphocyte counts may have an abnormal T cell immunity and the observed TCL may be a temporary suppression resulting from transient lymphopenia secondary to severe infections. In such cases, it is necessary to estimate the severity of the observed TCL by assessing thymic capabilities. In this study, patients clinically suspected of SCID were evaluated for lymphocyte subsets analysis, naive T cells and T cell receptor excision circles (TREC). Patients with transient lymphopenia had detectable TREC levels and normal naive T cells subsets. Normalization of absolute lymphocyte counts, and T cells was seen in the patients after a short duration. The authors highlight the importance of detailed immunological investigations in an infant with severe infections and lymphopenia before labeling the infant as SCID.
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- 2018
12. Clinical, Immunological, and Molecular Findings in Four Cases of B Cell Expansion With NF-κB and T Cell Anergy Disease for the First Time From India
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M. R. Lokeshwar, Mukesh Desai, Aparna Dalvi, Priyanka Kambli, Jahnavi Aluri, Prasad Taur, Maya Gupta, Jenna R.E. Bergerson, Michael J. Lenardo, Manasi Kulkarni, Manisha Madkaikar, and Snehal Mhatre
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lcsh:Immunologic diseases. Allergy ,Male ,0301 basic medicine ,T-Lymphocytes ,Immunology ,India ,CARD11 ,Disease ,medicine.disease_cause ,NF-κB ,Autoimmunity ,GOF mutation ,03 medical and health sciences ,chemistry.chemical_compound ,medicine ,Humans ,Immunology and Allergy ,polyclonal B cell lymphocytosis ,B cell ,Original Research ,Clonal Anergy ,B-Lymphocytes ,Whole Genome Sequencing ,biology ,business.industry ,Autoimmune Lymphoproliferative Syndrome ,NF-kappa B ,Infant ,medicine.disease ,CARD Signaling Adaptor Proteins ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Guanylate Cyclase ,Polyclonal antibodies ,Child, Preschool ,Gain of Function Mutation ,Autoimmune lymphoproliferative syndrome ,Primary immunodeficiency ,biology.protein ,Female ,lcsh:RC581-607 ,business ,Signal Transduction - Abstract
B cell expansion with NF-κB and T cell anergy (BENTA) is a rare primary immunodeficiency disorder caused by mutations in the CARD11 gene and results in constitutive NF-κB activation in B and T cells. Affected patients present with polyclonal expansion of B cells at an early age with splenomegaly, lymphadenopathy, and mild autoimmunity. Here, we discuss four BENTA cases with unusual clinical manifestations not previously reported. All patients showed previously reported gain-of-function mutations (G123S, G123D, and C49Y) in the CARD11 gene. Severe autoimmune manifestations were noted for the first time in all our patients.
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- 2018
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13. Adenosine Deaminase Deficiency with a Novel Gene Mutation
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Jahnavi Aluri, Antony Terrance, Manisha Madkaikar, and Maya Gupta
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0301 basic medicine ,Adenosine Deaminase ,Lymphocyte ,Genetic enhancement ,03 medical and health sciences ,0302 clinical medicine ,Adenosine deaminase ,Agammaglobulinemia ,medicine ,Missense mutation ,Humans ,Reticular dysgenesis ,Severe combined immunodeficiency ,medicine.diagnostic_test ,biology ,business.industry ,Immunologic Deficiency Syndromes ,Complete blood count ,medicine.disease ,Adenosine deaminase deficiency ,030104 developmental biology ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Immunology ,Mutation ,biology.protein ,Severe Combined Immunodeficiency ,business ,030215 immunology - Abstract
To the Editor: Adenosine deaminase (ADA) deficiency is a rare autosomal recessive form of severe combined immunodeficiency disorder (SCID) caused by mutations in the ADA gene [1]. ADA-SCID is associated with both Bearly^ and Blate onset^ of presentation due to wide variability in the genetic mutations. No data is available about its incidence in India, but it is expected to be high due to high consanguinity. We are presenting a case of ADA-SCID from India. Informed consent was obtained from the participants included in the study. A 6-mo boy, born of 2 degree consanguineous marriage presented with respiratory infections, failure to thrive, developmental delay and dysmorphic features like hairy forehead, frontal bossing, fused eyebrows and clinodactyly. Chest radiograph showed an absence of thymic shadow, the anterior end of ribs and costochondral junctions appeared normal. Complete blood count (CBC) revealed a low lymphocyte percentage (6 %) and absolute lymphocyte count (ALC – 771/ cumm) with normal blood indices (Hb 9.3 g/dl, platelet count 266 x10/L). Serum immunoglobulin and uric acid levels were normal. Patient was immunized as per schedule including BCG at birth. The infectious work up was negative. RBCADA levels were low (0.7 U/g Hb) [2]. The lymphocyte subset analysis (LSS) by flowcytometry showed marked reduction in absolute counts of T (655/cumm), B (23/cumm), NK (85/cumm) cells. Sanger sequencing revealed a novel homozygous missense mutation (c.42 T > C; p.Leu14Pro) in exon 2 ofADA gene and was predicted deleterious using SIFT, Polyphen and Panther software. Parents were carrier for the same mutation. This change was not detected in a statistically significant number of control samples. As reported, depletion of T, B and NK cells with severe infections and developmental delay was noted in our patient at an early age [3]. A low ALC and TBNK phenotype is associated with ADA deficiency, Purine Nucleoside Phosphorylase (PNP) deficiency and Reticular Dysgenesis. The present case showed low ADA levels with normal uric acid levels and normal ANC on CBC; hence, was evaluated for ADA gene studies. Developmental delay and neurological abnormalities are well described in ADA–SCID, however, the dysmorphic features with clinodactyly seen in this child is rare and not been reported in the literature. It is difficult to say if any other additional genetic abnormalities were responsible for the same, however we could not evaluate it by cytogenetic studies. Though, live vaccines are contraindicated in ADA–SCID, no immunization complication was observed in our patient. Murine ADA gene studies revealed that H15D mutation alters an ability of zinc to activate a water molecule postulated to play a role in the catalytic mechanism [4]. The L14P in our patient is located just before H15D mutation and may result in similar effects. Apart from hematopoietic stem cell transplantation (HSCT) or gene therapy or enzyme replacement therapy, supportive measures like immunoglobulin supplements, prophylactic antifungals, and antibiotic must be initiated immediately after diagnosis to reduce the morbidity [5]. Inspite of adequate supportive therapy our patient expired due to respiratory complications. Typical cl inical manifesta t ions, lymphopenia, immunophenotypic studies and RBC ADA levels provide a clue towards the underlying ADA deficiency that can be * Manisha Madkaikar madkaikarm@icmr.org.in
- Published
- 2015
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