AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency.

BACKGROUND: Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. METHODS: Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. RESULTS: The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. CONCLUSIONS: There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed.

Dynamic Changes of IFN-γ-producing Cells, TGF-ß and Their Preidctive Value in Early Outcomees of Renal Transplantation.

BACKGROUND: A growing body of evidence demonstrated an immune etiology as well as nonimmune mechanisms for episodes of clinical acute rejection and long-term allograft dysfunction. OBJECTIVE: To investigate the correlation of IFN-γ-producing cells and TGF-ß with incidence of clinical acute rejection in living-related and unrelated kidney allogarft recipients during the first post-transplant year. METHODS: This multi-center study was performed on 57 kidney allograft recipients from living-related (n=20) and unrelated (n=37) donors between April 2011 and September 2012 and who were followed prospectively for a mean period of one year. Peripheral blood samples were collected from all patients pre-transplantation and at days 14, 30 and 90 after transplantation; PBMCs were used as responding cells in enzyme-linked immunosorbent spot (ELISPOT) assay to measure the frequency of IFN-γ-producing cells after stimulation with donor lymphocytes. Additionally, TGF-ß levels were measured in cell culture supernatants of ELISPOT assay. RESULTS: During the follow-up period, 45 (79%) patients were diagnosed with stable graft function (group A); 12 (21%) experienced clinical acute rejection episodes (group B). The frequency of IFN-γ-producing cells was significantly (p<0.001) higher in the rejection group in all three times after transplantation. Also, post-transplantation comparison for TGF-ß showed a significantly (p<0.001) higher contents in group A vs. group B. Comparing the post-transplantation levels of TGF-ß and mean numbers of IFN-γ- producing cells between groups A and B demonstrated a continuous increment in TGF-ß and decreasing frequencies of IFN-γ-producing cells in group A vs. group B. CONCLUSION: Serial post-transplantation monitoring of IFN-γ-producing donor reactive cells during the first months is a clinically feasible approach for identification of kidney allogarft recipients at risk for ongoing immune-mediated graft damage and later graft loss.

Serum levels of interleukin (IL)-10, IL-17, transforming growth factor (TGF)-ß1, and interferon-γ cytokines and expression levels of IL-10 and TGF-ß1 genes in renal allograft recipients after donor bone marrow cell infusion.

BACKGROUND: Cytokine storm generated by an alloimmune response after transplantation can lead to either graft survival or rejection. The aim of this study was to evaluate the serum levels of interleukin (IL)-10, IL-17, transforming growth factor (TGF)-ß1, and interferon (IFN)-γ and expression levels of IL-10 and TGF-ß1 in renal allograft recipients with or without donor bone marrow cell infusion (DBMI). METHODS: We retrospectively followed 28 living unrelated kidney recipients, including 14 with and 14 without DBMI infusion for 2 years. Also, 14 healthy subjects were included as a normal control group. PBMC gene expression analysis for mRNA levels of IL-10 and TGF-ß1 cytokines relative to ß-actin as a reference gene was performed using quantitative fluorescence real-time polymerase chain reaction at the end of 2 years posttransplantation. Also, serum levels of IL-10, TGF-ß1, IFN-γ, and IL-17 in the 3 groups were measured by enzyme-linked immunosorbent assay at the same time. RESULTS: Both patient groups showed increased gene expression and serum content of IL-10 compared with normal controls. The expression levels were only significant between control patients and normal subjects (P=.02). Serum levels of IFN-γ and IL-17 were higher in untreated patients compared with normal controls (P=.03 and P=.07, respectively). DBMI patients showed significantly lower levels of serum TGF-ß1 and IL-17 compared with normal subjects (P=.05 and P=.06, respectively). Also, infused patients showed a positive correlation between circulating levels of IL-17 and IL-10 (r=0.692; P=.006), and an inverse correlation between serum creatinine and TGF-ß1 levels (r=-0.580; P=.03). CONCLUSION: The decreased levels of inflammatory cytokines besides IL-10 with increased TGF-ß1 levels and better allograft function with improved clinical outcomes were observed among infused patients, possibly indicating immunomodulatory effects of this approach in kidney allograft patients.

TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.

OBJECTIVE: We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients. PATIENTS AND METHODS: We analyzed the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20 controls). RESULTS: Patients with acute rejection episodes (ARE)-3/20 DBMI and 6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01). Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P < .0001, respectively). CONCLUSIONS: Higher levels of sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

Plasma sCD26 and sCD30 levels in cutaneous leishmaniasis.

CD26 and CD30 are surface molecules expressed on activated Th1 and Th2 cells, respectively. It is, therefore assumed that plasma levels of CD26 and CD30 (sCD26 and sCD30) correlate with Th1 and Th2 response, respectively. In this study, plasma levels of sCD26 and sCD30 in patients with non-healing form of cutaneous leishmaniasis (CL) were measured and compared with the levels of sCD26 and sCD30 in patients with healing form of CL and healthy control volunteers. The results indicate that the plasma levels of sCD26 and sCD30 are significantly (p<0.05) higher in patients with non-healing form of CL than patients with healing form of CL or healthy control. No significant difference is seen in the levels of sCD26 and sCD30 in patients with healing form of CL in comparison with healthy control group. It is concluded that sCD30 might be used as an indicator of a Th2 response in patients with non-healing form of CL.

CD26 expression on CD4+T cells in patients with cutaneous leishmaniasis.

Surrogate marker(s) of protection in human leishmaniasis is not well defined. In this study, T helper 1 (Th1) and Th2 cytokine profiles and CD26 expression on CD4(+) T cells in peripheral blood mononuclear cells of patients with healing or non-healing forms of cutaneous leishmaniasis (CL) stimulated with Leishmania antigens were assessed. The level of interferon (IFN)-gamma production was significantly higher in patients with healing or non-healing forms of CL than in healthy controls, but it was not significantly different between the two patient groups. The level of interleukin-5 production was significantly higher in patients with the non-healing form of CL than in the two other groups. There was a significant increase in the level of CD26 expression on CD4(+) T cells in patients with healing (P < 0.001) or non-healing (P = 0.025) forms of CL compared with the control group, but no significant difference was seen between the two patient groups. A weak positive correlation was seen between IFN-gamma production and CD26 expression on CD4(+) T cells of patients with the healing form of lesion (r = 0.54, P = 0.008), but this correlation was not observed in patients with the non-healing form of CL (r = 0.53, P = 0.078). Surface CD26 is not correlated with the clinical manifestation of CL or IFN-gamma production. Therefore, CD26 is not a surrogate marker for IFN-gamma production in CL.

Microchimerism and renal transplantation: doubt still persists.

OBJECTIVE: We sought to study microchimerism in a group of kidney transplant recipients. MATERIALS AND METHODS: In this study, the peripheral blood microchimerism (PBM) after renal transplantation was retrospectively evaluated in 32 male-to-female recipients of living unrelated or cadaveric donor renal transplants. Using a nested polymerase chain reaction (PCR) amplification specific for SRY region of the Y chromosome, microchimerism was detected with a sensitivity of 1:1,000,000. Recipients were compared according to the presence of PBM, acute and chronic rejection episodes, type of allotransplant, recipient and donor age at transplantation, previous male labor or blood transfusion, allograft function (serum creatinine level), and body mass index. RESULTS: Among 32 recipients, 7 (21.9%) were positive for PBM upon multiple testing at various posttransplant times. All microchimeric recipients had received kidneys from living unrelated donors. No significant difference was observed with regard to other parameters. In addition the acute rejection rate in the microchimeric group was 3 (42%) versus 4 (16%) in the nonmicrochimeric recipients (not significant). CONCLUSION: Our results suggested better establishment of microchimerism after living donor kidney transplantation. However, doubt persists concerning the true effect of microchimerism after renal transplantation. It seems that microchimerism alone has no major protective role upon renal allograft survival.

Genetic association of interleukin-4, interleukin-10, and transforming growth factor-beta gene polymorphism with allograft function in renal transplant patients.

Despite advances in immunosuppressive therapy in the past decade, allograft rejection remains the primary cause for kidney graft failure. Cytokines are known to be important mediators in renal allograft outcome. The aim of the present study was to ascertain whether interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-beta cytokine gene polymorphisms contributed to kidney graft outcome. We evaluated single nucleotide polymorphism in IL-4 (-1098G/T, -590C/T, -33C/T), IL-10 (-1082A/G, -819C/T, -592A/C), and TGF-beta (codon 10 and 25) in 100 renal transplant recipients and 139 normal healthy control using polymerase chain reactions based on sequence-specific primers. Recipients were clinically characterized as rejection episode (RE) versus stable graft function (SGF). The results showed the frequencies of IL-4 -33 T allele in the RE, SGF, and control group to be 7%, 73%, and 28%, respectively. IL-10 -592 A allele frequency was 39% in RE, 26% in SGF, and 28% in the control group. TGF-beta codon 10 T allele was 39% in RE, 35% in SGF, and 53% in control group. In conclusion, this study suggested that some cytokine gene alleles reflected SGF among kidney transplant recipients.

Profile of cytokine gene polymorphisms in Iranian multiple sclerosis patients.

BACKGROUND: Cytokine gene polymorphisms have been extensively studied in association with different diseases. The role of cytokine gene polymorphisms in multiple sclerosis (MS), as a chronic immune-mediated neurodegenerative disease, has been previously reported. MATERIALS AND METHODS: DNA samples were collected from 44 patients with relapsing-remitting multiple sclerosis (RRMS) and 140 unrelated healthy subjects. All participants in this study were matched for ethnicity. Cytokine gene SNPs were determined using the PCR-SSP method. RESULTS: and discussion We found no significant differences between MS patients and controls in most of the studied cytokine genes. Remarkable results were obtained for IL-2 GG-330 genotype (P =0.06), IL-6 C-174 allele (P =0.06), CG and GG genotypes (P <0.001), and GG (P =0.02) and CG (P <0.001) haplotypes, and TNF-alpha A-238 allele (P <0.001), GG (P =0.003) and GA (P <0.001) haplotypes. These results suggest that polymorphic variations of these pro-inflammatory cytokines play an important role in susceptibility to MS.

Th1 and Th2 cytokine gene polymorphisms in two indigenous ethnic groups in Iran.

Cytokines are important immunomodulatory molecules in immune responses against microorganisms and also have an important role in the setting of disorders affecting immune system. Cytokine single nucleotide polymorphisms have been extensively studied in different normal populations as well as in relation to diseases. Some of these polymorphisms (SNP) affect cytokine gene transcription and expression. The polymorphisms of cytokine genes are potentially important as genetic predictors of the disease susceptibility and clinical outcome or as a tool for anthropological studies. In this study, samples have been collected from 261 healthy individuals located in two different regions of Iran (Tehran and Yazd). The allele and genotype frequencies of Th1 and Th2 cytokines SNP including interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been investigated, using the polymerase chain reaction-sequence-specific primer method. The allele and genotype frequencies in Tehran and Yazd populations were similar except for the IL-2, IL-4, IL-6 and IL-10. The IL-4 C allele, C/C -33 and T/T -1098 genotype were significantly more frequent in Tehran than in Yazd population (P = 0.04, P = 0.004 and P = 0.001, respectively). The G/A genotype of the IL-6 (nt565) and IL-10 (-1082) was significantly less frequent in Tehran than in Yazd population (P = 0.01 and P = 0.003, respectively). The GT haplotype of the IL-2 (-330, +166) was significantly less frequent in Tehran than in Yazd population (P = 0.0002). We have also compared our whole samples with the reported data from other countries showing that Iranian population have cytokine gene polymorphism profile similar to that of Caucasians, especially Italian population.

Th-1 cytokines gene polymorphism in human brucellosis.

Brucellosis is a worldwide zoonosis. Infection with Brucella species results in the activation of cell-mediated immune response. The interaction between Th1and Th2 cytokines determines the outcome of disease. Production of each cytokine is in turn affected by genetic factors. In this study, we investigated the possible association between Th1 cytokines gene polymorphism and brucellosis. Different genotypes of TNF-alpha, IFN-gamma and IL-2 were determined by polymerase chain reaction-sequence-specific primer in 47 patients with brucellosis and in 166 healthy controls. Allele frequencies of these genotypes were compared using the chi2 test. The results showed a significant difference in the TNF-alpha genotype GG/GG in patients in comparison with controls (76.7% vs. 21%) (P = 0.001, OR = 12.42, 95%CI 5.7-27.7). There was no significant difference in the frequency distribution of the IFN-gamma genotypes between two groups. IL-2 GG genotype at position -330 was about two times more common in cases than in controls, but the difference was not significant (10.6 vs. 4.6 P value = 0.09). This study shows that genetically low producers of TNF-alpha are possibly susceptible to brucellosis and raise doubt about the role of gene polymorphism of INF-gamma in brucellosis which was demonstrated in previous studies. It seems that patients with brucellosis did not have a defect in producing IL-2 with even a trend towards producing higher amounts of this cytokine.

Value of pretransplantation cytokine profiles for predicting acute rejection in renal transplant recipients.

Episodes of acute rejection may represent an important risk factor for the development of chronic allograft nephropathy. Various studies have shown that pretransplant cytokine profiles in recipient blood are associated with transplant outcome. Serum samples were collected 24 hours before transplantation from 57 patients (38 men and 19 women of age 36 +/- 5 years) receiving kidneys from unrelated living donors. Additional samples were collected at 1 and 2 weeks after transplantation, as well as during every rejection episode. The immunosuppression consisted of a cyclosporine, prednisolone, and mycophenolate mofetil. Among the transplanted patients, 19 (33.3%) individuals experienced an acute rejection episode based on an increased level of serum creatinine and blood urea nitrogen during the first 14 days after transplantation. TGF-beta, IL-2 and IFN-gamma serum levels were determined by an ELISA method using Bindermed system kits. The mean concentration of TGF-beta before transplantation tended to be lower among patients with acute rejection episodes compared to those with stable graft (75,265 versus 85,394 pg/mL; P = .34) and at 1 week after transplantation (77,558 versus 84,390 pg/mL), although the differences were not significant. Among patients with rejection the mean IL-2 concentration was significantly higher before, at 1 week, and at 2 weeks after transplantation (15.0 versus 6.8 pg/mL, P = .005; 19.0 versus 4.9 pg/mL, P = .001; and 21.1 versus 4.7 pg/mL, P = .0001). The mean concentration of IFN-gamma was significantly higher pre- and at 1 and 2 weeks posttransplantation in patients with acute rejection episodes (161.1 versus 65.2, 175.6 versus 66.5 and 173.7 versus 77.1 pg/mL, all P < .001). In conclusion, evaluation of Th1 cytokines before transplantation may represent valuable predictive marker for an acute rejection episode.

TH1/TH2 cytokine analysis in Iranian renal transplant recipients.

The pretransplant cytokine profile of donor and recipient blood and tissues may be associated with transplant outcome. A Th1 response is generally associated with transplant rejection, while a Th2 response may lead to tolerance and stable graft survival. A total of 56 (37 male and 19 female) patients of mean 36 +/- 5 years were candidates for living unrelated kidney transplantation. Serum samples were collected 24 hours pretransplantation as well as at 1 and 2 weeks posttransplantation. Immunosuppression consisted of cyclosporine, prednisolone, and mycophenolate mofetil. Among the transplanted patients, 19 (33.9%) individuals experienced an acute rejection episode, as proven by biopsy, as well as an increased serum creatinine and blood urea nitrogen, within 14 days after transplantation. We determined serum concentrations of interleukin (IL) 2 and interferon (IFN)-gamma for Th1 and IL4 and IL10 for Th2 by an enzyme-linked immunosorbent assay method (Bender med system kits, Germany). Among Th1 cytokines, the mean concentration levels for groups with versus without acute rejection were: IL-2 pretransplant 15 pg/mL vs 6.8 pg/mL, respectively (P = .005); IL-2 at 1 week, 19 pg/mL vs 4.85 pg/mL, respectively (P = .001); IL-2 at 2 weeks, 21.1 pg/mL vs 4.65 pg/mL, respectively (P = .0001); IFN-gamma pretransplant 161.1 pg/mL vs 65.2 pg/mL, respectively (P = .001); IFN-gamma at 1 week, 175.6 pg/mL vs 66.5 pg/mL, respectively (P = .001); and IFN-gamma at 2 weeks, 173.7 pg/mL vs 77.1 pg/mL (P = .001). IL-2 and IFN-gamma levels were significantly higher in the group with acute rejection versus those without acute rejection. In conclusion, these data suggest that cytokine analysis, especially of Th1 cytokines, might be a valuable prognotic index of kidney transplant outcome.

Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia.

Chronic myelogenous leukaemia (CML) is a disorder of the haematopoietic stem cell that results in malignant expansion of myeloid cells with a cytogenetic abnormality, and translocation between chromosomes 9 and 22, known as the Philadelphia chromosome. It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing CML. In this regard, T helper types 1 and 2 (Th1 and Th2) cytokines and their gene polymorphism seem to be important. Overall expression and secretion of cytokines are dependent, at least in part, on genetic polymorphism (nucleotide variations) within the promoter region or other regulatory sequences of cytokine genes. The majority of polymorphisms described are single nucleotide polymorphism (SNPs). The objective of this study was to analyse the genetic profile of Th1 and Th2 cytokines in 30 Iranian patients with CML and 40 healthy subjects. In the patients and control subjects, the allelic and genotype frequencies were determined for the cytokine genes. All typing were performed with a polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. Allele and genotype frequencies were calculated and compared with those of normal controls. The results showed that the most frequent genotypes in our patients were transforming growth factor (TGF)-beta TG/TG, interferon (IFN)-gamma AT, interleukin (IL)-4 CC at position -590, TT at position -33, and IL-10 ACC/ACC and ATA/ATA. In contrast, the genotypes TGF-beta CG/CG, IL-2 TT at position -330, IL-4 CT at position -590, CT at position -33, and IL-10 GCC/ACC were seen at much lower frequencies. The results suggest that production of TGF-beta in CML patients is higher and production of IL-4 and IL-10 is lower than in normal subjects.

Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4-year follow-up study.

In the present study the relation between human leukocyte antigen (HLA), optic neuritis (ON) and multiple sclerosis (MS) has been investigated in 56 Iranian patients (46 females and 10 males). HLA-A and -B typing by microlymphocytotoxicity method and HLA-DRB, DQA and DQB by polymerase chain reaction based on sequence specific primers method was performed for the selected patients with ON. The diagnosis of clinically defined MS (CDMS) was confirmed in 15 of them (26.7%) during their follow-up. HLA-A24 was significantly higher in ON patients, whilst A23, A26, and A30 showed a significant decrease in these patients. HLA-A10 and A26 were absent in CDMS patients and A2 and A11 were significantly decreased in ON and CDMS patients. HLA-B5, B51, B38, B27, and B35 were significantly increased in ON patients compared with control subjects. HLA-B44, B16 and B38 alleles were not present in CDMS patients. Regarding DR locus, the frequency of HLA-DRB1*15 and DRB1*04 has been increased in CDMS patients, whilst the frequency of HLA-DRB1*07 and *11 was much higher in ON patients. In DQA region, the most frequent allele in the MS patients was DQA1*0102, which was significantly higher than ON patients, and control group. The frequency of DQA1*0103 was significantly increased in both patients group. In DQB1, the frequency of DQB1*0602 increased significantly in the MS patients. In conclusion existence of common genetic basis for early manifestations of MS could be suggested.

The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis.

OBJECTIVES: To investigate HLA-DRB1, DQA1 and DQB1 allelic polymorphism in Iranian patients with pulmonary tuberculosis (PTB). METHODS: Forty patients with smear-positive PTB and 100 healthy individuals as a control group were studied for MHC class II allelic polymorphism by polymerase chain reaction with sequence-specific primers (PCR-SSP). The primer was supplied by biotest in the standard kit. DRB low resolution SSP and DQA, DQB intermediate resolution SSP was applied. RESULTS: The comparison of the patients and the control group showed a significant increase in the frequency of the HLA-DRB1*07 and DQA1*0101 alleles (OR 2.7, 95%CI 1.19-6.13, P = 0.025 and OR 2.66, 95%CI 1.15-6.44, P = 0.04, respectively) in the patient group. The frequency of DQA1*0301 and DQA1*0501 was also significantly decreased (OR 0.254, 95%CI 0.075-0.865, P = 0.033 and OR 0.53, 95%CI 0.3-0.95, P = 0.045, respectively) in the PTB patients. Concerning haplotype frequency, DRB1*11501, QDQA1*0103 and DQB1*0601 were increased, but this difference was not statistically significant. In the DQB1 locus, DQB1*0501 was non-significantly over-represented. CONCLUSIONS: HLA-DRB1*07 and HLA-DQA1*0101 appeared to be the predisposing alleles and HLA-DQA1*0301 and 0501 the protective alleles in our patients with TB.

Major histocompatibility complex class I and II antigens frequencies in Baloch ethnic group living in the southeast region of Iran.

BACKGROUND: Human leukocyte antigens have become key components to investigate the genetic relationships between populations. OBJECTIVE: The aim of this study was to determine the genetic diversity of HLA class I and II alleles among the Baloch ethnic group of southeastern in comparison with the Parsi ethnic group, thereby establishing a database for further investigations on the ancestry and genetic factors contributing to complex diseases in this region. MATERIALS AND METHODS: Thirty unrelated Balochi individuals from southeast Iran and 108 Parsi unrelated individuals were serologically typed using standard microcytotoxicity assays with commercial and local trays. RESULTS: The most frequent class I alleles of the Baloch ethnic group were HLA-A01 (53.3%), -A02 (30%), -A09 (23.3%), -A11 (20%), -A23 (23.3%), -B05 (53.3%), and -B08 (26.7%). The class II alleles more frequently observed were HLA-DR1 (26.7%), -DR2 (43.3%), -DR3 (20%), -DR4 (33.3%), -DR7 (26.7%), -DR11 (33.7%), -DRw52 (83.3%), -DRw53 (36.7%), -DQ1 (46.7%), -DQ2 (20%), and -DQ3 (40%). In contrast with the Parsi ethnic group, the frequencies for the following alleles were significantly higher in Baloch than Parsi. HLA-A01, -A23, -A25, -B05, -B08, -B16, -B17, -B60, -DR14, -DQ4, and -DQ7. In contrast, the frequencies of HLA-Cw4 and -DQ3 alleles in the Parsi were significantly higher than the Baloch ethnic group. CONCLUSIONS: This first study of HLA in widely dispersed areas of Iran represents an important resource for investigators in the fields of transplantation immunology and population genetics.

Analysis of microsatellite polymorphism around the HLA-B locus in Iranian patients with Behçet's disease.

We have previously suggested that in a Japanese population the susceptible locus for Behçet's disease (BD) is HLA-B51 itself. To confirm this finding in another population, we performed HLA class I typing using the PCR-SSP method and analyzed eight polymorphic markers distributed within 1100 kb around the HLA-B gene using automated sequencer and subsequent automated fragment detection by fluorescent-based technology with the DNA samples of 84 Iranian patients with BD and 87 healthy ethnically matched controls. As a result, three microsatellite alleles (MICA-A6, MIB-348, C1-4-1-217) and HLA-B51 were found to be strongly associated with BD. Of these alleles HLA-B51 is the most strongly associated allele. There were no alleles that were increased in allele frequency at any microsatellite loci centromeric of MICA or telomeric of HLA-B51. Therefore, HLA-B51 was confirmed to be by far the most strongly associated gene with BD in an Iranian population.

HLA class I genotyping including HLA-B*51 allele typing in the Iranian patients with Behçet's disease.

It is well known that Behçet's disease (BD) is strongly associated with human leukocyte antigen (HLA) B51 in many ethnic groups. However, there has been no published report as yet with respect to this association among the Iranian people. Furthermore, since it is now known that the B51 antigen can be encoded by 21 alleles, B*5101-B*5121, we performed HLA-B*51 allele typing as well as HLA class I genotyping of 48 Iranian patients with this disease. As a result, the frequency of the B*51 allele was significantly higher (62.1%) in the patient group as compared with the ethnically matched control group (31.8%) (Pc=0.067, R.R.=3.51). In the genotyping of B*51 alleles, 33 out of the 36 B*51-positive patients possessed B*5101 and the remaining 3 carried B*5108. This study revealed that Iranian patients with BD also had a strong association with HLA-B51. In addition, this significantly high incidence of HLA-B*51 was found to be caused by an increase in both the HLA-B*5101 and HLA-B*5108 alleles. However, there was no significant difference in the HLA-B*51 allelic distribution between the patient and control groups.