Lack of association between alopecia areata and HLA class I and II in a southeastern Brazilian population

Abstract: Background: Alopecia areata (AA) is a common disorder of unknown etiology that affects approximately 0.7% to 3.8% of patients among the general population. Currently, genetic and autoimmune factors are emphasized as etiopathogenic. Studies linking Human Leukocyte Antigens (HLA) to AA have suggested that immunogenetic factors may play a role in the disease's onset/development. Objectives: To investigate an association between AA and HLA class I/II in white Brazilians. Methods: Patients and control groups comprised 33 and 112 individuals, respectively. DNA extraction was performed by column method with BioPur kit. Allele's classification was undertaken using the PCR-SSO technique. HLA frequencies were obtained through direct counting and subjected to comparison by means of the chi-square test. Results: Most patients were aged over 16, with no familial history, and developed partial AA, with no recurrent episodes. Patients showed a higher frequency of HLA-B*40, HLA-B*45, HLA-B*53 and HLA-C*04 compared with controls, although P was not significant after Bonferroni correction. Regarding HLA class II, only HLA-DRB1*07 revealed statistical significance; nevertheless, it featured more prominently in controls than patients (P=0.04; Pc=0.52; OR=0.29; 95%; CI=0.07 to 1.25). P was not significant after Bonferroni correction. Conclusions: The development of AA does not seem to be associated with HLA in white Brazilians, nor with susceptibility or resistance. The studies were carried out in populations with little or no miscegenation, unlike the Brazilian population in general, which could explain the inconsistency found.

HLA among Brazilian patients with spontaneous chronic urticaria and positive autologous serum skin test / HLA em brasileiros com urticária crônica espontânea e teste cutâneo do soro autólogo positivo

BACKGROUND: An association between class I and II alleles of the major histocompatibility complex and idiopathic chronic urticaria has previously been observed in different populations, but there are still no studies on Brazilian populations in this regard. OBJECTIVE: The involvement of the major histocompatibility complex classes I and II (loci A, B and DR) in Brazilian patients with idiopathic chronic urticaria and a positive autologous serum skin test was investigated and compared with a healthy population group. METHODS: DNA was extracted from the blood of 42 patients with idiopathic chronic urticaria and major histocompatibility complex classes I and II alleles were determined using the polymerase chain reaction and a laboratory test for oligonucleotide hybridization using a single-filament probe. The frequencies of these alleles in patients with chronic urticaria were compared with the frequencies in 1000 genetically unrelated voluntary blood donors from the same region of Brazil. The diagnosis of idiopathic chronic urticaria was based on the patients' clinical history and routine laboratory tests. Only the patients with positive autologous serum skin test were selected. The allele distribution resulted from the patient and control groups were analyzed using odds ratios and 95% confidence intervals. RESULTS: No statistically significant differences were found between the positive autologous serum skin test patients with chronic urticaria and the control group. CONCLUSIONS: We found that in this population group, there was no specific association between the HLA alleles studied and chronic urticaria. We believe that further population studies are needed in order to investigate the possible existence of this association.

FUNDAMENTOS: A associação entre os alelos do MHC classe I e II e a urticária crônica idiopática tem sido previamente constatada em diferentes populações, sendo que na população brasileira ainda não existem estudos a este respeito. OBJETIVOS: Foi estudado o envolvimento do MHC classe I e II (locci A, B e DR) em pacientes brasileiros com urticária crônica idiopática e teste cutâneo do soro autólogo positivo, comparando-se com um grupo populacional saudável. MÉTODOS: O DNA foi extraído do sangue de 42 pacientes com urticária crônica idiopática e o MHC classe I e II determinado por reação em cadeia da polimerase e teste laboratorial de hibridização de oligonucleotídeo com sonda de filamento único. A freqüência destes alelos em pacientes com urticária crônica idiopática foi comparada com a de 1000 doadores de sangue voluntários e geneticamente não relacionados, da mesma região do Brasil. O diagnóstico de urticária crônica idiopática foi baseado na história clínica do paciente e exames laboratoriais de rotina; foram selecionados apenas os pacientes com teste cutâneo do soro autólogo positivo. O resultado da distribuição alélica entre o grupo de pacientes e o grupo controle foi analisado através do odds rate com o cálculo do intervalo de confiança de 95% (95% IC). RESULTADOS: Não foram encontradas diferenças com significância estatística entre os pacientes com urticária crônica teste cutâneo do soro autólogo positivos e o grupo controle. CONCLUSÕES: Verificamos que neste grupo populacional estudado não houve associação específica entre os alelos HLA estudados e a urticária crônica; acreditamos na necessidade de outros estudos populacionais, para podermos verificar a possível existência desta associação.

Correlation between serum anti-MICA antibodies and chronic rejection in renal transplant recipients / 中华器官移植杂志

Objective To explore the relationship of serum anti-MICA antibody and development of chronic rejection (CR) after renal transplantation. Methods The enrolled 105 patients included 43 cases of CR, and 62 cases of functioning renal allograft as controls. Data including PRA level before transplantation, HLA mismatch, cold ischemic time, SCr at discharge, immunosuppressive regimen,and months after transplantation were analyzed. Blood samples were collected immediately after grouping for anti-MICA antibodies, SCr determination. Acute rejection episodes and renal allograft function which was evaluated by △SCr/M [(SCr at present - SCr at discharge) /months after transplantation) were compared between anti-MICA-antibody positive patients and anti-MICA-antibody negative patients. Results There was no significant difference in gender, age, HLA mismatch, cold ischemic time, immunosuppressive regimen, SCr at discharge, months after transplantation between CR and control groups (P＞0.05). Serum creatinine level and number of antiMICA-antibody positive patients in CR group were significantly increased as compared with those in control group (P＜0.01 ). Acute rejection episodes during the first 3 months after transplantation in anti-MICA-antibody positive patients were significantly more than those in anti-MICA-antibody negative patients (P＜0.05),and the △SCr/M in the former was higher than that in the latter (8.3 +3.6 vs 2.4 ± 2.6, P＜0.05). Conclusion Humoral immunoreaction mediated by MICA partly participates the development of CR after renal transplantation. MICA antibody is a risk factor affecting long-term allograft function.

Expression of anti-MICA antibodies and its influence on acute rejection and allograft function of sensitized renal recipients in early post-transplant course / 中华器官移植杂志

Objective To explore the expression of anti-MICA antibodies and evaluate its influence on acute rejection and renal function in early period after renal transplantation. Methods A total of 29 sensitized subjects (PRA＞20 %) were enrolled in this study. All the patients underwent protein A immunoabsorption treatment and the expression of anti-MICA antibodies was detected before and after treatment. Triple immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil (MMF) and steroid was given to prevent graft rejection. The correlation between the expression of anti-MICA antibodies and acute rejection or serum creatinine (SCr) level was analyzed.Results The expression of anti-MICA antibodies was detected in 8 candidates (27. 6 % ,8/29) ,and 6 kinds of anti-MICA antibodies simultaneously expressed were found in one individual, 3 kinds in one case,and sole kind in 6 patients. There was no significant difference in acute rejection rate between positive anti-MICA antibodies group and negative group [37.5 % (3/8) vs 38. 1% (8/21), P＞0.05). The positive expression rate of anti-MICA antibodies in the recipients with PRA ≥40% was higher than that in those with PRA ＜40% [43. 8 % (7/16) vs 7. 7 % (1/13),P＜0.05]. The SCr level in patients positive for anti-MICA antibodies was markedly higher than that in those negative anti-MICA antibodies at the 1st week postoperatively ( 135.4 ± 21.4 vs 108. 6 -+ 31.6 μmol/L, P＜0.05). The SCr level in the patients with positive anti-MICA antibodies, however, was reduced to the normal range at the 2nd week after surgery (P＞0.05). The levels of anti-MICA antibodies were continuously decreased in the candidates undergoing protein A irnmunoadsorption treatment. Conclusion Higher expression of anti-MICA antibodies exists in sensitized recipients and possesses an influence on the recovery of renal function in early postoperative period. Protein A immunoadsorption can eliminate anti-MICA antibodies effectively in sensitized recipients.

Patogenia de las espondiloartropatías seronegativas

Se estudió la función que desempeña el antígeno leucocitario humano (HLA-B27) en la patogénesis de las espondiloartropatias seronegativas. Se describió detalladamente la zona de unión de péptidos de la molécula conocida como «bolsón 45». Como hipótesis actuales en el surgimiento de la enfermedad se discutieron la mímica molecular entre bacterias artritogénicas y HLA-B27, la positividad del HLA-B27 y la persistencia de las infecciones enterobacteriales, HLA-B27 factores modificantes y el modelo del péptido artritogénico. Se explicó la función de la célula T CDB+ en el desencadenamiento de la enfermedad y su control por los linfocitos T CD4+.

The function of HLA-B27 in the pathogenesis of seronegative spondyloarthropathies was studied. The zone of union of the peptides of the molecule known as «big pocket 45» was described in detail. The molecular mimicry between arthritogenic bacteria and HLA-B27, the positivity of HLA-B27 and the persistance of enterobacterial infections, the HLA-B27 modifying factors, and the model of arthritogenic peptide were discussed as present hypotheses connected with the appearance of the disease. The function of the CDB-positive T-cell in the outbreak of the disease, as well as its control by the CD4-positive T-lymphocytes was explained.

Association of HLA-A Alleles with Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To explore the potential association of HLA-A alleles and genetic susceptibility with systemic lupus erythematosus (SLE). Methods Polymerase chain reaction-sequence specific primer (PCR-SSP) was used to analyze the distribution of HLA-A alleles among 106 patients with systemic lupus erythematosus and 122 healthy persons. Results Nineteen out of twenty-four kinds of HLA-A alleles were found from the specimens, including 18 kinds in SLE specimens, and 15 kinds in control specimens. Among them, HLA-A*11 allele was positively associated with SLE (RR = 2.4380, EF = 0.1502, ?2 = 12.2440, P = 0.0005, Pc = 0.0095). For A*01 and A*24, although the P values were less than 0.05, the Pc values were more than 0.05 (0.9462 or 0.2356, respectively). Conclusions The results indicate that HLA-A*11 may be the susceptible allele or may be closely linked with the susceptible genes in Chinese SLE patients.

Impact of HBV/C gene mutation G87 on HIA-I expression of host cells / 解放军医学杂志

Objective To study the impact of HBV/C gene G87 mutation on HLA-I expression of host cells. Methods HBV wild-type genome plasmid was reconstructed by site-directed mutagenesis technique and subcloning technique into expression vector of G87 mutant (EBO-G87) and expression vector of wild type (EBO-WT), which were transfected into HepG2 cells via liposome technique,respectively.The transfected cells were stained with murine mAb anti-HLA-ABC conjugated directly to FITC, and HLA-I expression on their membranes was analyzed by flow cytometry. Results The constructed vectors of EBO-WT and EBO-G87 were identified by restriction enzyme digestion and nucleotide sequencing. The mean fluorescence intensity of HLA-I expression on transfected cells with EBO empty vector was at low level(2.3). It was elevated remarkably to 18.8 by EBO-WT, while that of EBO-G87 was increased to 10.5. Conclusion Two strains of HBV may up-regulate the expression of HLA-I, and G87 mutation of C gene may affect the expression level of HLA-I on host cells.