Association of HLA-DRB1, DQA1 and DQB1 alleles and haplotypes with common variable immunodeficiency in iranian patients

Common Variable Immunodeficiency [CVID] is an antibody deficiency syndrome that often co-occurs in families with selective IgA deficiency [IgAD]. This study was designed to investigate the frequency of DR and DQ loci of HLA class II region in common variable immunodeficiency [CVID] patients. Fifteen Iranian patients with CVID or IgAD [mean age 14.6 +/- 5.4, range 4-25 years; 9 male and 6 female] and 63 healthy controls were studied. Establishment of B-lymphoblastoid cell lines was performed using Epstein-Barr-virus [EBV] immortalization technique and HLA alleles were typed using polymerase chain reaction based on sequence specific primers [PCR-SSP]. DRB1 alleles including DRB1 *04 [p=0.03] and DRB1 *11 [p=0.01] significantly showed higher frequency in the studied subjects. In contrast, DRB1 *301 [p=0.04] and DRB1 *07 [p=0.02] alleles were negatively associated with CVID. For DQB1 and DQA1 loci, DQB1 *0302 [p=0.047] and DQA1 *03011 [p=0.001] demon-strated high frequency in cases, while DQB1 *0201 [p=0.02] and DQA1 *0201 [p=0.01] were detected to be low when compared to controls. Haplotype analysis indicated that frequency of DRB1*04-DQB1*03011-DQA1 *03011 [p=0.02], DRB1 *11-DQB1 *03011-DQA1 *0505 [p=0.047], DRB1 *11-DQA1 *0505 [p=0.04] and DRB1*04-DQA1*03011 [p=0.02] haplotypes were significantly higher in patient group, while only the frequency of the DRB1 *07-DQA1 *0201 haplotype gene was statistically lower in control group [p=0.02]. According to the results, it could be deduced that the HLA-DR and DQ loci may contribute to the pathogenesis of CVID or they might be considered as suitable markers for the possibility of the occurrence of this genetic defect

IL-1, IL-1R and TNFalpha gene polymorphisms in Iranian patients with multiple sclerosis

Different research groups have extensively studied the associations of cytokine gene polymorphisms in different diseases. The role of cytokines gene polymorphisms in multiple sclerosis [MS], as a chronic Immune-mediated neurodegenerative disease, has been previously reported in the various populations. For determining pro-inflammatory cytokine gene polymorphisms, 100 relapsing remitting multiple sclerosis [RRMS] Iranian patients and 140 normal individuals as control enrolled in this study. DNA of each sample was extracted by a modified salting out method. Cytokine single gene nucleotide polymorphisms including IL-1alpha -889, IL-1beta [-511 and +3962], IL-1R pst1 1970, IL-1RA mspal 11100, and TNF-alpha [-308 and -238] were determined by using the PCR-SSP method. The results of our data indicate the decrease in frequency of IL-1alpha TC-889 genotype [p=0.002], IL-1beta TC +3962 genotype [p=0.004], IL-1R T pst1 1970 allele [p= 0.0001], IL-1 RA TC Mspa1 11100 genotype [p=0.009], TNF-alpha A-308 allele [p=0.0002] and AG genotype [p=0.00001] in the patients group versus normal subjects. On the other hand the frequency of IL-1alpha TT -889 genotype [p=0.028], IL-1R C pst1 1970 allele [p=0.0001] and CC genotype [p=0.00006], TNFalpha G -308 allele [p=0.0002] and GG genotype [p=0.000001] decreased significantly in the patients versus normal subjects. These results suggest that polymorphic variations of these pro-inflammatory cytokines may play an important role in susceptibility of Iranian multiple sclerosis patients

HLA-DRB1, DQA1 and DQB1 alleles and haplotypes frequencies in Iranian healthy adult responders and non-responders to recombinant hepatitis B vaccine

Different studies have demonstrated that a small proportion of healthy individuals receiving the hepatitis B [HB] vaccine do not produce protective levels of anti-HB antibody, a phenomenon which could be linked to certain human leukocyte antigen [HLA] class-II alleles or haplotypes. The present study was undertaken to determine the frequency of HLA class-II alleles in Iranian healthy adult responders and non-responders to HB vaccine. Twelve non-responders [anti-HBs antibody < 10 IU/L] and 46 responders [anti-HBs antibody > 100 IU/L] were tissue typed for HLA class-II. HLA-DRB1, DQB1 and DQA1 alleles were determined using polymerase chain reaction based on sequence specific primers [PCR-SSP] technique. Accessibility to excess amount of genomic DNA was possible using Epstein-Barr virus [EBV]-transformed B-cells established from all vaccinees. Our results demonstrated increased frequencies of HLA- DRB1*07, DRB1*03, DRB1*04, DQB1*0201, DQA1*0201 alleles and HLA- DRB1*07/DQB1*0201/DQA1*0201 and DRB1*04/DQB1*0302/DQA1*03011 haplotypes in the non-responder group. Comparison between responders and non-responders revealed only a significant difference for DQB1*0201 allele [p < 0.05]. These findings confirm the association of certain HLA alleles and haplotypes with the lack of antibody response to HB vaccine in an Iranian population