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The presence in a recipient of antibodies directed against donor-specific antigens represents a major obstacle to transplantation. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques, and old and new drugs are currently used for desensitizing these patients. Desensitization may either occur before transplantation, at the time of transplantation, or after transplantation according to whether physicians are dealing with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivities and specificities, and different advantages and drawbacks. The targets of the drugs used to desensitize are B cells, plasma cells, the antibodies themselves, and, finally, the complement that is the final actor causing tissue disruption. B cells are relatively easy to target; targeting the plasma cell is more difficult. Indeed, several new drugs are also used in randomized trials to defeat plasma cells. Antibodies may be removed easily, but their removal is often followed by antibody rebound. The complement is not easy to defeat and new drugs are currently used for this aim. Overall, despite difficulties, desensitization is currently possible in many cases, to obtain a safe and successful transplantation.

Introduction: Hematopoietic Progenitor Cell Transplantation is currently a treatment for different malignant and non-malignant hematological disorders, which is performed when there is a recipient with an identical or haploidentical donor for the genes of the Major Histocompatibility Complex. In the absence of a compatible family donor, we have created the Volunteer Donor Program with HLA System typing, who have expressed their consent to be donors and share the alleles of the human lymphocyte system encoded on the short arm of chromosome six. Materials and methods: The present study is a descriptive, observational, and cross-sectional study that presents the results of the search for volunteer donors for recipients without a family donor in the Panama Dono Program and its application in Panama. Results: Of the family groups studied, which included recipients and family donors, a total of 783 persons studied voluntarily accepted to be unrelated donors and their HLA typing incorporated into the Panama Dono Program. A total of 321 patients without an identical or haploidentical donor in their family group have been searched for unrelated donors in the Program and the first recipient was transplanted with a voluntary donor compatible in 16 genes of the Major Histocompatibility Complex in the Hospital del Niño. Conclusion: The National Transplant Laboratory of the Social Security Fund has managed to create the Program of Voluntary Donors of Hematopoietic Progenitor Cells called PANAMA DONO, which consists of 788 Panamanians who have expressed their consent. Currently a patient from the Hospital del Niño was transplanted in 2022 with this unrelated compatible donor modality. The identical compatibility of the recipient with the volunteer donor was 16 identical alleles of the Major Histocompatibility Complex. [ABSTRACT FROM AUTHOR]

The presence in a recipient of antibodies directed against donor-specific antigens represents a major obstacle to transplantation. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques, and old and new drugs are currently used for desensitizing these patients. Desensitization may either occur before transplantation, at the time of transplantation, or after transplantation according to whether physicians are dealing with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivities and specificities, and different advantages and drawbacks. The targets of the drugs used to desensitize are B cells, plasma cells, the antibodies themselves, and, finally, the complement that is the final actor causing tissue disruption. B cells are relatively easy to target; targeting the plasma cell is more difficult. Indeed, several new drugs are also used in randomized trials to defeat plasma cells. Antibodies may be removed easily, but their removal is often followed by antibody rebound. The complement is not easy to defeat and new drugs are currently used for this aim. Overall, despite difficulties, desensitization is currently possible in many cases, to obtain a safe and successful transplantation. [ABSTRACT FROM AUTHOR]

Guatemala is a country located in Central America, and while it is one of the most populated countries in the region, the genetic diversity of the population has been poorly analyzed. Currently, there are no analyses of the distribution of human leukocyte antigen (HLA) system alleles in mixed ancestry (i.e., ladino) populations in Guatemala. The HLA system exhibits the most extensive polymorphism in the human genome and has been extensively analyzed in a large number of studies related to disease association, transplantation, and population genetics (with particular importance in the understanding of diversity in the human population). Here, we present HLA typing data from 127 samples of unrelated individuals from the kidney transplant program of the San Juan de Dios General Hospital (Guatemala City) using a PCR-SSOP-based (PCR-sequence specific oligonucleotide probes) typing method. We found 16 haplotypes that accounted for 39.76 % of the total haplotype diversity, of which thirteen have been reported previously in Native American populations and three have been reported in European populations. The analyses showed no deviations from Hardy-Weinberg equilibrium, and admixture estimates calculated with k = 3 ancestral components showed that Native American was the most represented component, followed by the European component. The African component was less prominent in the Guatemala mixed ancestry sample in comparison to samples from other countries in Central America. The HLA-based admixture results for Central America showed a continuum in the distribution of Native American, European and African ancestries throughout the region, which is consistent with the complex demographic history of the region. [ABSTRACT FROM AUTHOR]

Interindividual clinical variability characterizes COVID-19 infection SARS-CoV-2 infection, ranging from no or mild symptoms in >95% of individuals to severe and life-threatening acute respiratory distress syndrome with bilateral pneumonia requiring intensive care unit monitoring in <0.5% of infected individuals. The host genetic background seems to determine the susceptibility and outcome in COVID-19 patients. Several relevant genetic variants and risk genes have been identified, relating to blood type, HLA system, angiotensin converting enzyme and other proteins, cytokines, and other host genetic signals and immune system's specific response. On the other hand, emerging new variants of the COVID-19 virus with enhanced transmissibility/infectivity and immune escape ability pose new risks, especially if they are going to have an impact on the efficacy of currently available vaccines. All these issues relating to the impact of genetics on COVID-19 selectivity are herein reviewed. [ABSTRACT FROM AUTHOR]

Copyright of Der Nephrologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The human leukocyte antigen (HLA) system is a major part of the human immune system and has an impact on tumor initiation, tumor progression, and immunosurveillance. Renal cell carcinoma tumors are considered to be immunogenic. Therefore, we studied the allele frequencies of four gene loci (HLA-A, -B, -C, and HLA-DR) in a cohort of German renal cell carcinoma (RCC) patients and in healthy controls. HLA-A-C were determined using serological methods, whereas HLA-C12, C14, C16, C18, and HLA-DR were characterized through the use of standard molecular biological methods. The occurrence of the HLA-C*12 allele was significantly increased in German RCC patients compared with healthy controls ( P < 0.005; Fisher's exact test), whereas the occurrence of the HLA-DRB1*04 allele was significantly reduced in RCC patients compared with healthy controls ( P < 0.05; Fisher's exact test). However, the presence of allele HLA-C*12 was not significantly associated with 10 year overall survival. We suggest that the frequency of HLA alleles can affect development of RCC and could add knowledge as predictive marker for future immunotherapies. [ABSTRACT FROM AUTHOR]

The major histocompatibility complex system is the most polymorphic gene cluster of the mammal genome. In humans, this is a genomic locus known as the human leukocyte antigen (HLA) system. The HLA encodes mostly immune-associated proteins whose main effect is the presentation of antigens to the immune cells. Thus, it is clear that it is essential for to the proper function of the immune response against pathogens and strongly implicated in the development of autoimmune diseases. Nonetheless, there are hundreds of polymorphisms of HLA- DRB1 which have been associated with different autoimmune disorders as well as with immune response to infection and vaccines. It is possible that the interaction of specific HLA with pathogenic antigens is one of the keys favoring (or protecting) toward the development of an autoimmune disease. In the era of personalized medicine, it would be of great help to build a map of the genomic risk of each individual to evaluate the risk of developing an autoimmune condition. [ABSTRACT FROM AUTHOR]

La autoinmunidad se caracteriza por una pérdida de la tolerancia inmunológica que produce la destrucción de células y tejidos propios. El sistema del complejo mayor de histocompatibilidad posee una fuerte asociación con las enfermedades autoinmunes aunque determinados genes que codifican para citoquinas y moléculas coestimuladoras incrementan la susceptibilidad genética. Estudios de concordancia entre gemelos monocigóticos demuestran el papel de los factores ambientales en la aparición de las enfermedades autoinmunes. A pesar de los avances científicos producidos en esta área de investigación, los mecanismos subyacentes de estas afecciones son desconocidos. El objetivo deeste trabajo es exponer de forma sintetizada el papel de los factores genéticos, inmunológicos y ambientales en la autoinmunidad.The autoimmunity is characterized by a loss of immunologic tolerance producing the destruction of cells and own tissues. The major complex system of histocompatibility has a close association with the autoimmune diseases although determined genes codifying for cytokines and co-stimulators molecules increase the genetic susceptibility. Concordance studies among monozygotic twins demonstrate the role of environmental factors in appearance of autoimmune diseases. Despite the scientific advances achieved in this research field, the underlying mechanisms of these affections are unknown. The objective of present paper is to expose in a summarized way the role of the genetic, immunologic and environmental factors in autoimmunity.

Allogeneic tissue transplantation is one of the most effective treatments for several diseases and injuries, in particular, malignant and non-malignant hematological conditions. Following this procedure, transplanted tissue encounters various complications, one of the most serious being graft-versus-host disease (GvHD). The management of GvHD directly affects the success of transplantation and the survival rate of the patient; therefore, many studies have focused on GvHD prevention and control. This review briefly explains the transplantation process, causes of graft rejection, and importance of the human leukocyte antigen system. Initially, we address the pathophysiology and immunobiology of GvHD, the cells involved in this complication, the differences between chronic and acute GvHD, and the importance of graft-versus-leukemia. Interestingly, various types of immune cells are involved in GvHD pathogenesis. After explaining how these cells affect the GvHD process, we discuss the studies conducted to control and reduce GvHD symptoms.

The development of red blood cell alloantibodies is induced by the transfusion of antigen incompatible blood products. Similarly, incompatibility between maternal and foetal erythrocyte antigens may be the cause of alloantibody occurrence in pregnant women. The presence of antibodies may have clinical consequences such as haemolytic transfusion reactions or haemolytic disease of the foetus and new-born. In transfusion medicine, antibodies present certain complications in the selection of suitable blood products, especially in patients who require long-term RBC transfusion therapy. Individuals exposed to RBC alloantigens can be divided into responders (producing alloantibodies) and non-responders (without alloantibody production). The aim of this work was to summarize current knowledge concerning alloimmunization based on immunogenetic predisposing risk factors, focusing on the occurrence of specific alloantibodies in association with particular MHC HLA Class II molecules. [ABSTRACT FROM AUTHOR]

Foi feita análise e revisão de estudos populacionais de associação entre antígenos HLA e a esclerose múltipla (EM). Há evidências de que os genes HLA, principalmente os de classe II, das sub-regiões DR e DQ possam estar envolvidos. O haplótipo DRB1*1501.DQA1*0102.DQB1*0602 referente ao fenótipo DR2.Dw2.DQ6 foi encontrado em associação positiva em vários estudos realizados em populações caucasóides. O desequilíbrio de ligação entre os genes DR e DQ dificulta o reconhecimento da contribuição individual de cada alelo. A heterogeneidade de critérios diagnósticos da EM constitui importante fator metodológico que dificulta a comparação entre os diversos estudos. A padronização dos critérios diagnósticos e dos métodos laboratoriais empregados, assim como a análise individual de grupos de pacientes com formas clínicas diferentes, são medidas que provavelmente permitirão avaliação mais precisa dos fatores genéticos envolvidos no desenvolvimento da EM.Review of studies about HLA antigens and multiple sclerosis (MS). The HLA system, in special class II antigens, subregions DR and DQ, is probably involved in the immunopathogenesis of MS. Haplotype DRB1*1501.DQA1*0102.DQB1*0602, corresponding to phenotype DR2.Dw2.DQ6, is positively associated with MS in several caucasoid populations. Clinical heterogeneity of MS, as well as different diagnostic criteria adopted by investigators are potential sources of confusion and may lead to discrepant results. A better standardization of clinical and laboratorial methodology, appropriate subdivision of patients with different clinical forms of MS, may allow a more accurate evaluation of the role of genetic factors in the pathogenesis of MS.

REM sleep behavior disorder is a sporadic sleep disorder. From association studies it is known that a genetic component can be postulated because of the association with some genetic neurodegenerative disorders, e.g. inherited Parkinson syndromes and spinocerebellar ataxia type 3. In contrast to non-REM parasomnias just a weak link to the HLA system was shown. Most evidence for a genetic component was recently seen in a large cohort of REM sleep behavorial patients who were found to have an increased familial prevalence compared to age- and sex-matched controls. With regard to this background it can be postulated that REM sleep behavorial disorder is modulated by genetic factors, which are not suitable predictive markers [ABSTRACT FROM AUTHOR]

Copyright of Collegium Antropologicum is the property of Croatian Anthropological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Parasomnias comprise a great variety of motor phenomena during sleep. A genetic background was postulated many years ago based on twin studies and cohort studies. A few molecular genetic approaches were performed analysing the association to the HLA system. For sleep walking and REM behaviour disorder an association with the HLA system was shown. HLA DQB1*0501 and DQB1*0402 were the loci associated with sleep walking. REM behaviour disorder was also shown to have an association with the HLA DQB1* 0501 locus. Other sleep disorders, which were formerly classified as parasomnias according to ICSD-1 and are not classified any longer as parasomnias according to ICSD-2, include sleep talking and bruxism as shown by twins and family heredity studies. For these sleep disorders further evidence for genetic loci or even single genes are lacking. Nocturnal enuresis showed clear heredity but chromosomal loci or even an association to the aquaporin gene were not verified. Since there is not enough evidence that parasomnias are either complex genetic or monogenetic work is needed to gather more epidemiological data. Further linkage studies will elucidate the impact of single genes on the clinical expression of parasomnias. The identification of genetic susceptibility genes or single disease-causing genes will help in the development of novel biologically based treatment options. [ABSTRACT FROM AUTHOR]

Preliminary pharmacogenetic data suggest that germline genetic informations might be of value in individualizing disease-modifying antirheumatic drugs (DMARDs) therapy in various autoimmune chronic inflammatory diseases. Either DMARDs small molecules (DMARDs-SM) or DMARDs biological therapies (DMARDs-BT) might be selected for their lower toxicity or better efficacy based on single-nucleotide polymorphisms (SNPs) of genes governing the metabolism of drugs, or the response of immune cells to proinflammatory molecules, or the proinflammatory molecular activity of immune cells. Data available for one DMARDs-SM, methotrexate, suggest that a careful assessment of the SNPs of four enzymes involved in the folate metabolism allow one to construct a genetic index of toxicity (toxicogenetic index) that might be employed in daily practice to find the patient's most at risk. Only the full knowledge of the various gene polymorphisms controlling the phenotypic manifestations of the inflammatory–immunological milieu of each rheumatic disease will allow one to obtain the clear definition of a personalized medicine. Few different cytokine gene SNPs seem to be of importance in determining the susceptibility to diseases, or the aggressiveness of diseases. The role of genetics in affecting a possible clinical response to DMARDs-BT targeting specific inflammatory molecules or their receptors still has to be defined. However, the available data suggest that cytokine (and/or receptors) gene SNPs might indeed play a role in determining the biological effects, hence the clinical effectiveness of DMARDs-BT. Crucial to this aim will be the prospective analysis of clinical benefits and safety on the basis of the at baseline stratification of gene SNPs in each chronic inflammatory rheumatic disease before starting any new DMARDs-SM or DMARDs-BT.The Pharmacogenomics Journal (2007) 7, 2–9. doi:10.1038/sj.tpj.6500396; published online 9 May 2006 [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by fibroblast expansion, and tissue remodeling. It is considered a multifactorial disease but the possible involved genes are largely unknown. Interestingly, studies regarding the possible role of major histocompatibility complex (MHC) are scanty and show contradictory results. In this study, we evaluated the polymorphisms of the MHC, locus HLA-B, -DRB1, and -DQB1 in a cohort of 75 IPF patients and 95 controls by using PCR and hybridization with sequence-specific oligonucleotide probes. In addition, we examined the effect of bronchoalveolar lavage (BAL) from IPF patients with different MHC haplotypes on alveolar epithelial growth rate by WST-1 cell viability assay and on epithelial apoptosis by flow cytometry and by cleaved caspase-3 in cell homogenates. Three haplotypes were significantly increased in IPF: (1) HLA-B*15-DRB1*0101-DQB1*0501 (OR=10.72, CI=1.43–459.6; pC=0.011); (2) HLA-B*52-DRB1*1402-DQB1*0301 (OR=4.42, CI=1.21–24.1; pC=0.024); and (3) HLA-B*35-DRB1*0407-DQB1*0302 (OR=4.73, CI=1.53–19.5; pC=0.005). BAL from patients with the later haplotype significantly reduced epithelial growth rate (∼30%) and caused epithelial cell apoptosis assayed by cleaved caspase-3 (351.7±16.5 pg/106 cells versus 264±24 from controls, and 274±36.8 and 256.5±10.7 from the other haplotypes; P<0.05), and DNA breaks labeling by flow cytometry (23.7±6.9% versus 3.1±0.7% from controls, and 6.5±0.6% and 7.6±1.2% from the other two haplotypes; P<0.01). These findings suggest that some MHC polymorphisms confer susceptibility to IPF, which might be related with the induction of epithelial cell apoptosis, a critical process in the development of the disease. [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO) is a frequent complication following total hip arthroplasty (THA). At present, the etiology HO is unknown, however, genetic predisposition may be a cause of HO in individuals in whom no risk factors can be detected. The goal of this study was to investigate the HLA system, searching for any correlation with the presence of HO after THA. Thirty-five patients of Sicilian origin were operated on between January 1997 and January 1999 for cementless THA under regional anesthesia. The entire series was divided into three groups and all underwent histocompatibility typing. Group I was made up of 10 patients who presented with HO Brooker grades 1 and 2 after THA; group 2 comprised 7 patients affected by grades 3 and 4 HO after THA; and group 3 was made up of 18 subjects who presented with one or more preoperative risk factors for developing peri-prosthetic HO before undergoing THA. No positivity for HLA-B27 antigen was observed, but there was as an increase in HLA-B18 (with respect to that in the Sicilian population) in patients with HO following THA. The main conclusion from the study is that there is a strong correlation between the presence of the antigens HLA-A2 and HLA-B18 in patients with HO grades 3 and 4. [ABSTRACT FROM AUTHOR]

Background/Aims: An association of Class II HLA-DR8 antigen is reported in patients with serum antimitochondrial antibodies (AMA)-positive primary biliary cirrhosis (PBC); no information exists as to an association with AMA-negative PBC. We compared the frequency of HLA Class II genes in AMA-positive and AMA-negative PBC patients and healthy controls.Methods: Genomic DNA was extracted from the blood of 154 AMA-positive and 26 AMA-negative Caucasian PBC patients and from 216 healthy Caucasian controls and tested for the alleles at two HLA Class II loci, DRβ1 and DQβ1.Results: Higher allele frequencies of HLA-DRβ1*08 and DQβ1*04 were found in the AMA-positive PBC patients versus controls (14.9% vs. 6.5%, odds ratio (OR)=3.3, global P=0.03 and 14.4% vs. 6.5%, OR=2.6, global P=0.002). All patients positive for DRβ1*0801 were positive for the DQβ1*0402 allele, delta score=22 for AMA-positive patients, 11 for controls. In AMA-negative PBC, the frequency of DRβ1*08 and DQβ1*04 was 0%, significantly different from the AMA-positive patients (P=0.05, P=0.05).Conclusions: AMA response may identify a group of PBC patients with a distinctive expression of the disease with the response associated with a gene(s) in the class II region of the major histocompatibility complex on the short arm of chromosome 6. [Copyright &y& Elsevier]

The highly heterogeneous symptomatology and unpredictable progress of COVID‑19 triggered unprecedented intensive biomedical research and a number of clinical research projects. Although the pathophysiology of the disease is being progressively clarified, its complexity remains vast. Moreover, some extremely infrequent cases of thrombotic thrombocytopenia following vaccination against SARS‑CoV‑2 infection have been observed. The present study aimed to map the signaling pathways of thrombocytopenia implicated in COVID‑19, as well as in vaccine‑induced thrombotic thrombocytopenia (VITT). The biomedical literature database, MEDLINE/PubMed, was thoroughly searched using artificial intelligence techniques for the semantic relations among the top 50 similar words (>0.9) implicated in COVID‑19‑mediated human infection or VITT. Additionally, STRING, a database of primary and predicted associations among genes and proteins (collected from diverse resources, such as documented pathway knowledge, high‑throughput experimental studies, cross‑species extrapolated information, automated text mining results, computationally predicted interactions, etc.), was employed, with the confidence threshold set at 0.7. In addition, two interactomes were constructed: i) A network including 119 and 56 nodes relevant to COVID‑19 and thrombocytopenia, respectively; and ii) a second network containing 60 nodes relevant to VITT. Although thrombocytopenia is a dominant morbidity in both entities, three nodes were observed that corresponded to genes (AURKA, CD46 and CD19) expressed only in VITT, whilst ADAM10, CDC20, SHC1 and STXBP2 are silenced in VITT, but are commonly expressed in both COVID‑19 and thrombocytopenia. The calculated average node degree was immense (11.9 in COVID‑19 and 6.43 in VITT), illustrating the complexity of COVID‑19 and VITT pathologies and confirming the importance of cytokines, as well as of pathways activated following hypoxic events. In addition, PYCARD, NLP3 and P2RX7 are key potential therapeutic targets for all three morbid entities, meriting further research. This interactome was based on wild‑type genes, revealing the predisposition of the body to hypoxia‑induced thrombosis, leading to the acute COVID‑19 phenotype, the 'long‑COVID syndrome', and/or VITT. Thus, common nodes appear to be key players in illness prevention, progression and treatment.

• HLA-A*02:11, HLA-B*15:17, HLA-A*24:03 and HLA-A*26:02 most potent in detecting SARS-CoV2 epitopes. • South Asians could recognize higher number of CD8-specific epitopes. • Europeans could identify higher number of CD4-specific epitopes. • Mutations in SARS-CoV2 are unlikely to alter T-cell mediated immunogenic responses. The SARS-CoV2 mediated Covid-19 pandemic has impacted humankind at an unprecedented scale. While substantial research efforts have focused towards understanding the mechanisms of viral infection and developing vaccines/ therapeutics, factors affecting the susceptibility to SARS-CoV2 infection and manifestation of Covid-19 remain less explored. Given that the Human Leukocyte Antigen (HLA) system is known to vary among ethnic populations, it is likely to affect the recognition of the virus, and in turn, the susceptibility to Covid-19. To understand this, we used bioinformatic tools to probe all SARS-CoV2 peptides which could elicit T-cell response in humans. We also tried to answer the intriguing question of whether these potential epitopes were equally immunogenic across ethnicities, by studying the distribution of HLA alleles among different populations and their share of cognate epitopes. Results indicate that the immune recognition potential of SARS-CoV2 epitopes tend to vary between different ethnic groups. While the South Asians are likely to recognize higher number of CD8-specific epitopes, Europeans are likely to identify higher number of CD4-specific epitopes. We also hypothesize and provide clues that the newer mutations in SARS-CoV2 are unlikely to alter the T-cell mediated immunogenic responses among the studied ethnic populations. The work presented herein is expected to bolster our understanding of the pandemic, by providing insights into differential immunological response of ethnic populations to the virus as well as by gaging the possible effects of mutations in SARS-CoV2 on efficacy of potential epitope-based vaccines through evaluating ∼40,000 viral genomes. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is often associated with additional autoimmune phenomena. However, data reported on the frequency of thyroid autoimmunity differ vastly. Therefore, the prevalence of thyroid autoantibodies was evaluated at a large pediatric diabetes center in Southern Germany. 2,305 determinations (TPO and TG, ELISA) were performed in 495 patients with type 1 diabetes (234 boys, 261 girls; age at last measurement: 15.4 ± 0.3 years, duration of diabetes 7.5 ± 0.2 years). The prevalence of elevated thyroid antibodies increased dramatically with age: from 3.7% in patients less than 5 years of age up to 25.3% in the age group 15–20 years (p < 0.0001). For children older than 10 years, girls were significantly more affected than boys (p < 0.0001). Thyroid autoimmunity tended to be more prevalent in the subgroup of patients with the HLA type DR3/DR4 compared to patients with other HLA types (p = 0.08). In children older than 10 years, basal TSH concentrations were significantly elevated in antibody-positive patients (p < 0.05). In conclusion, thyroid autoimmunity is prevalent in children and adolescents with type 1 diabetes. Adolescent girls and young women are especially affected. Yearly routine determinations of thyroid antibodies are therefore recommended.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Four and two male sibs of two separate families who had biopsy-proven membranoproliferative glomerulonephritis (MPGN) are presented. In the first family four sibs of the first-degree consanguineous marriage showed the clinical picture of nephrotic syndrome without hypocomplementaemia at initial laboratory findings. In the second family two affected sibs showed nephrotic and nephritic syndromes on admission. Family investigations showed normal serum complement, immunoglobulins, T-cell subsets, urine analysis, and serum biochemistry. HLA typing in the two families revealed a common antigen HLA A2 in all affected sibs. Some other reports give suggestive evidence of MPGN in siblings but this is the first report that showed the occurrence of MPGN in four sibs. Our data strengthened the concept that genetic factors are involved in the development of MPGN but additional immunogenetic studies will shed light on the genetic aspects of the disease. [ABSTRACT FROM PUBLISHER]

Chronic glomerulonephritis was diagnosed in 23 patients born in a small valley in Northern Italy and in five additional patients with one parent or a more remote ancestor born in the same area, all belonging to three potentially related families. Eighteen patients had biopsy-proven glomerulonephritis: 11 IgA nephropathy, 3 IgM nephropathy, 2 membranoproliferative type I, and 2 mesangial proliferative glomerulonephritis with isolated C deposits. Ten had clinical glomerulonephritis. A community screening programme discovered six additional related patients. Two underwent renal biopsy (1 IgA nephropathy; 1 focal glomerulosclerosis); four were diagnosed as having clinical glomerulonephritis. Genealogical investigation identified five deceased family members with diagnoses of chronic nephritis recorded on their death certificates. No environmental nephrotoxic factors were identified. Restriction fragment length polymorphism (RFLP) analysis of HLADR beta, HLA-DQ alpha and beta genes, and complement typing for C4A, C4B, and Bf polymorphisms were carried out for 29 patients, 168 healthy relatives, and 24 local controls. The frequency of HLA-Dw8.1 specificity, related to DR beta 8, DQ beta 3b, and DQ alpha la RFLPs, was significantly increased more in the affected and unaffected pedigree members than in Italian controls. [ABSTRACT FROM PUBLISHER]

The major genetic susceptibility to insulin dependent (Type 1) diabetes is determined by genes in the HLA chromosomal region. An increased relative risk for developing the disease is observed in subjects who are HLA A1, A2, B8, B18, B15, B40, CW3, Bf, DW3, DW4, DRW3, DRW4 positive. There is an additive relative risk in subjects who possess two 'high risk' HLA B alleles which has an important influence on the prevalence of the disease in sibships and possibly on the concordance rate in diabetic identical twins. There is also suggestive evidence that particular combinations of 'high risk' HLA B alleles are associated with increased or persistent antibody production which may reflect enhanced or differential susceptibility. Certain factors (e. g. HLA B7, DW2 and DRW2) are associated with a significantly reduced risk and may exert a 'protective' mechanism in Type I diabetes, by linkage disequilibrium with genes which reduce immune responsiveness. The significant increases and decreases in respect of the HLA B antigens are probably secondary to the corresponding HLA D and DRW associations which reflect a stronger linkage disequilibrium between the genes which determine these specificities and the putative genes which control susceptibility. Initial damage to the beta cells probably occurs a considerable time before the onset of symptoms and theoretically modification of the immune response early in the disease process may reduce the rate of beta cell destruction. [ABSTRACT FROM AUTHOR]

Abstract: We describe here the sequence and the molecular modeling of a new variant of HLA-A*32 allele officially named A*32:22. This novel allele has been detected in an Italian cord blood sample by sequence-based typing (SBT). The mutation (CAT →CGT), which has occurred at codon 151, at nucleotide position 524, implies an amino acidic change from Histidine to Arginine. Residue 151 is located on top of the molecule inside the region contacted by T cell receptor (TCR) and it is possibly involved in docking TCR. A positively charged residue is maintained on this position determining a slight change of electrostatic potential on the molecular surface. This suggests a limited functional relevance of the amino acid substitution encoded by A*32:22. [Copyright &y& Elsevier]

Recipients of allogeneic hematopoi¨etic stem cell transplantation (HSCT) incur the risk of graft-versus-host disease (GVHD) even when the donor is a sibling who shares the major histocompatibility antigens. Therefore, even the perfect HLA match does not represent the optimal genetic match between donors and recipients in HSCT. In addition to the HLA complex other genetic systems operate and affect the outcome of HSCT. These include minor histocompatibility systems (inducing bona fide allogeneic responses) as well as a series of functional polymorphisms in cytokines and chemokines and receptors genes . Among the items affecting the outcome of HSCT the incidence and severity of infections have an important impact. Polymorphisms of genes controlling both arms of the immune responses to pathogens (innate vs. cognate) are strong candidates for susceptibility factors to infection in allogeneic transplantation. These include the MHC alleles (HLA class I, class II, MIC) CD1, Toll and TLR genes MBP, MPO genes...). In addition to the NK alloreactivity induced by HLA class I epitopes mismatching (a common situation in HSCT) variations in the genotype of the KIR genes may also be encountered between the donor and the recipient leading to potentially harmful or beneficial combinations. An integrated knowledge of the role and hierarchy of the most important genetic factors (MHC and non-MHC) will provide the rationale for a comprehensive matching in HSCT . This short review provides a panorama of this strategic issue for further development of HSCT. [Copyright &y& Elsevier]