Frequency of HLA Class I and Class II Alleles in Patients with CVID from Turkey

Background: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. Certain gene loci are pointed out in several studies in CVID patients. Until now, monogenic defects have been identified in only 2-10% of CVID patients; therefore, association of the disease with HLA alleles may be important for elucidating immunological and genetic mechanisms behind CVID. The aim of this study is to investigate the relationship between CVID and HLA alleles. Methods: HLA class I/II alleles were analyzed in 65 patients with CVID and alleles that may be related to disease susceptibility were determined by comparing with 300 healthy controls. We also evaluated HLA allele frequencies in CVID patients with gastrointestial system (GIS) involvement and autoimmune manifestations. Results: When compared with controls, frequencies of B*27, B*35, C*04, and DRB1*04 alleles were significantly different in patients with CVID (p < .05). Frequencies of C*12, DRB1*13, and DRB1*15 alleles were more frequent in controls, indicating protective alleles (p < .05). There was a statistically significant difference for DQ2 and DQ8 haplotypes between patients with GIS involvement and controls. Conclusion: In comparison with literature, distinctive HLA alleles found in our study may originate from the diversity in gene pool between the populations. These data may provide clues for disease susceptibility

Lymphocyte Subgroups and KREC Numbers in Common Variable Immunodeficiency: A Single Center Study

Common variable immunodeficiency (CVID) results in defective B cell differentiation and impaired antibody production and is the most common symptomatic primary immunodeficiency. Our aim was to evaluate the correlation among B cell subgroups, κ-deleting recombination excision circle (KREC) copy numbers, and clinical and immunological data of the patients with CVID, and evaluate the patients according to classifications currently available to define the role of KREC copy numbers in the diagnosis of CVID. KREC analysis was performed using a quantitative real-time polymerase chain reaction assay, and B cell subgroups were measured by flow cytometry. The median age of the patients (n = 30) was 25 (6–69) years. Parental consanguinity ratio was 33%. The median age at diagnosis was 15 (4–59), and follow-up period was 6 (1–37) years. CD19+ and CD4+ cell counts at the time of diagnosis were low in 66.7% and 46.7% of the patients, respectively. CD19+ cell counts were positively correlated with KREC copy numbers in patients and healthy controls. CD19+ cell counts and KREC copy numbers were significantly reduced in CVID patients compared to healthy controls as expected. KRECs are quantitative markers for B cell defects. We found low CD4+ cell numbers, recent thymic emigrants, and lymphopenia in some of the patients at diagnosis, which reminds the heterogeneity of CVID’s etiology. In this study, a positive correlation was shown between CD19+ cell counts and KREC copy numbers. Low KREC copy numbers indicated B cell deficiency; however, high KREC copy numbers were not sufficient to rule out CVID

Mutations in ANKS6 cause a Nephronophthisis‐Like Phenotype with End Stage Renal Disease

<p>Nephronophthisis (NPHP) is one of the most common genetic causes of chronic kidney disease (CKD); however the underlying genetic abnormalities have been established in less than 50% of cases. We performed genome-wide analysis followed by targeted re-sequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 as the cause of an NPHP-like phenotype. Furthermore, we identified 4 additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic glomerulonephritis, interstitial nephritis or unknown etiology. We demonstrated expression of ANKS6 in human embryonic kidneys and showed that both total and active β-catenin were increased in pre-cystic tubuli in Cy/+ rats, indicating strong activation of the Wnt pathway</p

Mutations In Anks6 Cause A Nephronophthisis-Like Phenotype With Esrd

Nephronophthisis (NPHP) is one of the most common genetic causes of CKD; however, the underlying genetic abnormalities have been established in <50% of patients. We performed genome-wide analysis followed by targeted resequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 associated with an NPHP-like phenotype. Furthermore, we identified four additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic GN, interstitial nephritis, or unknown etiology. Immunohistochemistry in human embryonic kidney tissue demonstrated that the expression patterns of ANKS6 change substantially during development. Furthermore, we detected increased levels of both total and active beta-catenin in precystic tubuli in Han:SPRD Cy/+ rats. Overall, these data indicate the importance of ANKS6 in human kidney development and suggest a mechanism by which mutations in ANKS6 may contribute to an NPHP-like phenotype in humans.WoSScopu

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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