Sık Görülen Değişken İmmün Yetmezlik Tanısı Olan Hastalarda Hla Sınıf I ve Hla Sınıf Iı Allellerinin Sıklığının Araştırılması
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Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disease characterized by poor response to vaccination and recurrent infections with B cell differentiation and antibody production defects. Although the etiological factors of this disease are not fully known, the common phenotype-genotype correlations in families with consanguineous marriages and variability of its prevalence among societies indicate specific gene loci susceptible to disease. Until now, monogenic genetic deficiencies have been identified in only 10% of CVID patients; therefore, the association of this disease with HLA alleles, a genetic factor, is important in terms of elucidating the immunological and genetic mechanisms of the disease. In this study; HLA class I and class II alleles were studied in CVID patients, disease-related gene regions were investigated and alleles that could cause disease susceptibility were determined by comparing with 300 healthy controls. Sixty-five patients who were diagnosed with CVID in Department of Immunology of Department of Pediatrics of Faculty of Medicine of Hacettepe University were included in the study. The patient group was divided into 2 groups: patients with gastrointestinal involvement(31 patients) and patients without gastrointestinal involvement(34 patients) and compared with the control group. DQ2 and DQ8 haplotypes, which are additional genetic factors to aid in the diagnosis of celiac disease, have been evaluated in patients with gastrointestinal involvement. HLA Class I (A, B and C) and Class II (DRB1, DQB1 and DQA1) alleles were studied in the Luminex device by DNA-based Sequence Specific Oligonucleotide method. In this study, 13 alleles that may be associated with CVID are defined. Four of these alleles have previously been reported in the literature. Six alleles thought to be protective alleles have also been reported. When compared with healthy controls, HLA B*16, HLA B*27, HLA B*35 and HLA C*04 alleles were significantly different at p <0.05 significance level. In addition, the more common observation of HLA C*12 allele in healthy controls than the patient group indicates the presence of a protective allele. HLA DRB1*04 showed a high frequency in the patient group in accordance with the literature. HLA DRB1*13 and HLA DRB1*15 alleles are commonly observed in the control group, indicating the presence of protective alleles. The frequencies of DQB1*0101, DQB1*0254, DQB1*0305, DQB1*0501, DQB1*0502, DQA1*0106, DQA1*0302 ve DQA1*0501 alleles were significantly higher than the healthy control group(p <0,05, %95 GA). In addition, the more frequent occurrence of DQB1 * 0604, DQA1 * 0102 and DQA1 * 0505 alleles in healthy controls compared to the patient group indicates the protection of these alleles. No significant results were obtained for DQ2 and DQ8 haplotypes in 31 patients with gastrointestinal findings. However, 4 of these 31 patients are celiac patients. DQ8 was positive in 3 of these 4 patients. In 64 patients with CVID, 16 patients had autoimmune findings. In these patients, B * 27, DRB1 * 13, DQB1 * 0254, DQB1 * 0302 and DQA1 * 0201 alleles showed a higher frequency than healthy controls. It is thought that the HLA alleles, which are different from the literature, originate from the diversity in the gene pool between the populations. The obtained data provide diagnostic clues as well as expanding the genotyping criteria for diagnosis of the disease.