Relationship between human leukocyte antigen-DRB1 and autoimmune hepatitis type I in Chinese patients

AIM: To analyze the association of human leukocyte antigen (HLA)-DRB1 with autoimmune hepatitis type I (AIH) among Chinese patients in the Shanghai area. METHODS: In 32 patients and 48 healthy controls, polymerase chain reaction amplified with sequence-specific primers (PCR-SSP) was performed to elucidate the relevance of certain alleles or polymorphic sequences of HLA-DRB1 with autoimmune hepatitis. RESULTS: The HLA-DRB1 typing by PCR-SSP showed that DR4 had a significantly increased frequency among patients with AIH versus that of healthy controls (46.9 vs 20.8%; relative risk = 3.35, P = 0.014). In the subtypes of DR4, there was a trend of an increase in the gene frequency of DRB1*0405 in patients with AIH versus that of healthy controls (21.9 vs 6.3%, P = 0.04, but corrected P (Pc) = 0.08). In addition, our analysis indicated a significant increase in the alleles frequency encoding Leu-Leu-Glu-Gln-Lys-Arg (LLEQRR) from the third hyperpolymorphic region (HVR3) of DR4 in the patients with AIH (86.7% of DR4 positive patients vs 40.0% in DR4 positive controls, P = 0.016, Pc = 0.028, relative risk (RR) = 9.75). CONCLUSION: Type I AIH among Chinese patients is associated with HLA-DR4. There is a relevance of type I AIH and LLEQRR sequence within the third hyperpolymorphic region of the DRB1 allele.     

Aplastic Anemia in a Patient with Cronkhite-Canada Syndrome

Cronkhite-Canada syndrome (CCS) is a rare polyposis disorder accompanied by alopecia and onychodystrophy. A 63-year-old man with a history of CCS and repeated embolism developed progressive thrombocytopenia and mild anemia. Laboratory testing, a bone marrow examination, and magnetic resonance imaging of the spine resulted in a diagnosis of concurrent aplastic anemia (AA). Paroxysmal nocturnal hemoglobinuria (PNH)-type cells were detected in a peripheral blood specimen. In addition, human leukocyte antigen (HLA) included DRB1*15:01 and DRB1*15:02. Mesalazine was discontinued in consideration of possible drug-induced pancytopenia. Immunosuppressive therapy ameliorated both the gastrointestinal symptoms of CCS and pancytopenia. A common autoimmune abnormality might underlie both CCS and AA.     

Effect of perioperative steroid therapy on the postoperative course of patients with oesophageal cancer

BACKGROUND: Perioperative steroid therapy is often used in oesophageal cancer surgery and we evaluate the effect of this therapy on the secretory leukocyte protease inhibitor levels in the lungs (a major antiprotease in the conducting airways) and postoperative course in oesophageal cancer patients. METHODS: Twenty-one patients operated on for oesophageal cancer in 2003-2004 were treated with perioperative steroid therapy (250 mg of methylprednisolone intravenously 1 h before the operation). Fifteen consecutive patients operated on in 2002 served as a control group. Secretory leukocyte protease inhibitor in bronchoalveolar lavage fluid and the postoperative course in the two groups were compared. RESULTS: The mortality rate was 0% and there was no significant difference in the morbidity rate between the two groups. Days of intubation and systemic inflammatory response syndrome were significantly shorter for the steroid group. The bronchoalveolar lavage fluid secretory leukocyte protease inhibitor level was significantly higher in the steroid group than in the control group on postoperative days 2 and 3. The secretory leukocyte protease inhibitor level on postoperative day 3 was remarkably lower for the patients intubated for > or = 5 days and for those with pulmonary complications. CONCLUSION: Perioperative steroid therapy increased the bronchoalveolar lavage fluid secretory leukocyte protease inhibitor level and reduced the days of intubation and systemic inflammatory response syndrome in patients with oesophagectomy.     

Distribution of KIR genes in the Croatian population

The KIR locus with genes involved in immune processes is among the most polymorphic and structurally diverse human loci. KIR genes encode activating and inhibitory receptors that differ in specificity for HLA class I ligands and signaling potential. These receptors are expressed principally by natural killer (NK) cells and subpopulations of T cells. This study represents the first report of the distribution of KIR genes, KIR genotypes and KIR/HLA pairs in 121 unrelated healthy Croatian individuals. Twenty-three different genotypes were observed in the Croatian population and all 16 KIR genes known to date were found. The most frequent KIR genotype was the AA genotype. All individuals had at least one inhibitory KIR/HLA pair with the majority of individuals with three inhibitory KIR/HLA pairs. The most frequent KIR/HLA pair was the KIR2DL3/C1 group. Our results demonstrated the similarity of the Croatian population’s KIR repertoire with other Caucasian populations reported so far.     

Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study

Abstract

Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18?years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p?=?.00001) and those with DQX/X (p?≤?.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p?=?.018).

Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.     

Promotion and prevention of autoimmune disease by CD8+ T cells

Until recently, little was known about the importance of CD8+ T effectors in promoting and preventing autoimmune disease development. CD8+ T cells can oppose or promote autoimmune disease through activities as suppressor cells and as cytotoxic effectors. Studies in several distinct autoimmune models and data from patient samples are beginning to establish the importance of CD8+ T cells in these diseases and to define the mechanisms by which these cells influence autoimmunity. CD8+ effectors can promote disease via dysregulated secretion of inflammatory cytokines, skewed differentiation profiles and inappropriate apoptosis induction of target cells, and work to block disease by eliminating self-reactive cells and self-antigen sources, or as regulatory T cells. Defining the often major contribution of CD8+ T cells to autoimmune disease and identifying the mechanisms by which they alter the pathogenesis of disease is a rapidly expanding area of study and will add valuable information to our understanding of the kinetics, pathology and biology of autoimmune disease.     

False-positive reactivity of anti-human leukocyte antigen antibodies detected using the single-antigen bead assay

The single-antigen bead assay (SABA) demonstrates high sensitivity and specificity for detecting anti-human leukocyte antigen (HLA) antibodies. However, SABA may produce false-positive results for anti-HLA antibodies. Herein, we analyzed the data of patients with complement-dependent cytotoxic crossmatch^?/flow cytometric crossmatch^?/SABA^+/? results to determine false-positive results for anti-HLA antibodies. We also determined the prevalence of false-positive results by comparing false-positive data from our laboratory and national allele frequency data obtained with high-resolution HLA typing. For HLA-A, -B, -C, and -DR, a ratio of positive frequency to allele frequency of ≥3 in our laboratory was considered a false-positive result. For HLA-DQA1/DQB1 and HLA-DPA1/DPB1, we considered the positive frequency of ≥3 as a false positive result due to lack of haplotype frequency data. SABA results from 284 patients (78.0%) demonstrated false reactivity. The antibody against HLA-C*17:01 displayed the highest frequency ratio (298.3). If false-positive reactivity is suspected, results should be confirmed using different methods. If confirmation tests are unfeasible, comparing the allele frequency with the positive rate of detected anti-HLA antibodies and using a ratio ≥3 may facilitate the interpretation of SABA results. The positive rate of anti-HLA antibodies can be validated using the HLA allele frequency of the population to determine false-positive results.     

人类白细胞抗原新等位基因B*55:35的鉴定及家系调查

目的 鉴定人类白细胞抗原(human leukocyte antigen,HLA)基因B位点的1个新等位基因并调查其遗传情况.方法 应用聚合酶链反应-序列特异性寡核苷酸探针(polymerase chain reactionsequence specific oligonucleotide probe,PCR-SSOP) HLA分型技术发现1个疑似的新HLA等位基因,通过DNA测序鉴定其序列,并与同源性最高的HLA基因进行核苷酸序列比对,对携带者家系进行调查.结果应用PCR-SSOP进行HLA基因分型时,该样本HLA-B位点反应格局异常.DNA序列分析证实其为1个新HLA-B等位基因.与同源性最高的等位基因B*55:02比较,在第2外显子区域中有7个碱基发生改变,导致6个密码子发生了变化,造成2个氨基酸改变,即第69位的氨基酸由谷氨酸(Glu)变为甲硫氨酸(Met)、第70位的氨基酸由谷氨酸(Glu)变为丙氨酸(Ala).结论 发现并鉴定了HLA-B位点的1个新等位基因,GenBank注册号为FJ898284,被世界卫生组织HLA因子命名委员会正式命名为HLA-B* 55:35.