Alta concomitância de doenças autoimunes em um paciente com síndrome de Down / High concomitance of autoimmune diseases in a patient with Down syndrome

Objetivo: Pacientes com síndrome de Down (SD) apresentam maior prevalência de doenças autoimunes (DAI). No caso apresentado, chama atenção a elevada concomitância de DAI, a apresentação clínica das mesmas e a influência na saúde mental do paciente. Descrição do caso: Relatamos o caso de paciente masculino, 25 anos, cariótipo 47,XY+21, acompanhado pelo ambulatório de SD do HC/UFPR desde o nascimento, que até o presente momento apresentou cinco DAI associadas: vitiligo generalizado, alopecia areata, doença de Hashimoto, doença celíaca e psoríase. Nesse paciente, chama atenção as cinco doenças autoimunes concomitantes e a gravidade das doenças de pele. Foi realizada a fenotipagem da sua população linfocitária, obtendose numericamente: contagem normal de linfócitos T (CD3+) e de linfócitos T (CD8+); e contagem diminuída de linfócitos T (CD4+), células natural killer e linfócitos B. Foi realizada a sua tipagem HLA e observou-se a presença de alelos HLA-DQ2 e HLA-DR3 que, de acordo com a literatura, estão associados com o aparecimento de DAI. Aos 14 anos o paciente começou a apresentar sintomas da síndrome do pânico e episódios de transtorno obsessivo compulsivo. Comentários: A associação de fatores imunológicos e genéticos faz com que pacientes com SD possam ter concomitância de DAI. Profissionais de saúde que atendem pacientes Down devem estar atentos para tais doenças.

Objective: Patients with Down syndrome (DS) show a higher prevalence of autoimmune diseases (AIDs). In the case here described, the high concomitance of AIDs stands out, as does their clinical presentation and influence on the patient's mental health. Case description: We report the case of a male patient aged 25 years, karyotype 47,XY+21, followed from birth at the DS outpatient clinic at Hospital de Clínicas ­ Universidade Federal do Paraná. Up to the present moment, the patient presented five associated AIDs: generalized vitiligo, alopecia areata, Hashimoto's disease, celiac disease and psoriasis. In this patient, attention is drawn to the five concomitant AIDs and the severity of skin diseases. Phenotypic analysis of lymphocyte populations was obtained numerically, resulting in normal counts for T (CD3+) and T (CD8+) lymphocytes, and decreased counts for T lymphocytes (CD4+), natural killer cells and B lymphocytes. HLA typing was performed and the presence of HLA-DQ2 and HLA-DR3 alleles was observed ­according to the literature, these alleles are associated with the development of AIDs. At 14 years of age, the patient started to present symptoms of panic disorder and episodes of obsessive-compulsive disorder. Comments: The association of immunological and genetic factors leads patients with DS to have concomitant AIDs. Healthcare professionals who treat patients with DS should be aware of these diseases.

Association of and Polymorphisms with Risk of Systemic Lupus Erythematosus / 中华医学杂志(英文版)

Background@#Systemic lupus erythematosus (SLE) is an autoimmune disease under genetic control. Growing evidences support the genetic predisposition of HLA-DRB1 gene polymorphisms to SLE, yet the results are not often reproducible. The purpose of this study was to assess the association of two polymorphisms of HLA-DRB1 gene (HLA-DR3 and HLA-DR15) with the risk of SLE via a comprehensive meta-analysis.@*Methods@#This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case-control studies on HLA-DRB1 and SLE were searched from PubMed, Elsevier Science, Springer Link, Medline, and Cochrane Library database as of June 2018. Analysis was based on the random-effects model using STATA software version 14.0.@*Results@#A total of 23 studies were retained for analysis, including 5261 cases and 9838 controls. Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]: 1.60, 95% confidence interval (CI): 1.316-1.934, P = 0.129 and OR: 1.68, 95% CI: 1.334-2.112, P = 0.001, respectively). Subgroup analyses demonstrated that for both HLA-DR3 and HLA-DR15 polymorphisms, ethnicity was a possible source of heterogeneity. Specifically, HLA-DR3 polymorphism was not associated with SLE in White populations (OR: 1.60, 95% CI: 1.320-1.960, P = 0.522) and HLA-DR15 polymorphism in East Asian populations (OR: 1.65, 95% CI: 1.248-2.173, P = 0.001). In addition, source of control was another possible source for both HLA-DR3 and HLA-DR15 polymorphisms, with observable significance for HLA-DR3 in only population-based studies (OR: 1.65, 95% CI: 1.370-1.990, P = 0.244) and for HLA-DR15 in both population-based and hospital-based studies (OR: 1.38, 95% CI: 1.078-1.760, P = 0.123 and OR: 2.08, 95% CI: 1.738-2.490, P = 0.881, respectively).@*Conclusions@#HLA-DRB1 gene may be a SLE-susceptibility gene, and it shows evident ethnic heterogeneity. Further prospective validations across multiple ethnical groups are warranted.

HLA-DR3 antigen in the resistance to idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC.

Comprehensive study on the risk factors of hepatitis B virus intrauterine infection / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the risk factors of hepatitis B virus (HBV) intrauterine infection.</p><p><b>METHODS</b>Risk factors of HBV intrauterine infection were analyzed by nested case control study.</p><p><b>RESULTS</b>Data from univariate analysis revealed that risk factors of HBV intrauterine infection were positive results on HLA-DR3 (OR = 4.71, 1.62-13.66), HBV DNA (OR = 6.59, 2.72-15.97) and HBeAg (OR = 4.53, 1.93-10.64) in pregnant women, HLA-DR3 (OR = 3.91, 1.18-12.94) in newborn, HLA-I) R3 (OR = 5.96, 1.14-31.15) both in pregnant women and her newborns and HBV infection in placentas (OR = 2.51,1.12-5.60). Results from Multivariate unconditional logistics regression analysis showed that the risk factors of HBV intrauterine infection were positive in both HLA-DR3 (OR = 4.65, 1.44-15.05) and HBV DNA (OR = 6.56, 2.65-16.23) in pregnant women. However, there was no interaction between the two factors. The exposure rate of other factors did not reveal the difference in the two groups. With the increase of HBV DNA in pregnant women, the risk of HBV intrauterine infection was rising (chi2 = 16.74, P < 0.05).</p><p><b>CONCLUSION</b>Risk factors of HBV intrauterine infection were HLA-DR3 positive and HBV DNA positive in pregnant women but there was no interaction between the two factors. The risk of HBV intrauterine infection was increased along with the increase of HBV DNA in pregnant women.</p>

Symptomatic Sacroiliitis in Female Systemic Lupus Erythematosus / 영남의대학술지

We report a case of 17-year-old female with juvenile onset systemic lupus erythematosus Who developed symptomatic unilateral sacroiliitis. She had neither HLA-DR3 nir B27 antigens. Though sacroiliitis have been reported in mail SLE patient. it has been rarely reported in female patients. The rare coexistence of SLE and sacroiliitis. described in this case. may not be determined soley by genetic factors; sacroiliitis may be just an infrequent manifestation of SLE.

Kleine-Levin Syndrome: Two Cases

Kleine-Levin syndrome (KLS) is characterized by recurring episodes of hypersomnia, megaphagia, and abnormal behavior. We report two cases of KLS. Two boys, aged 18 (case 1) and 17 (case 2), had recurrent episodes of hyper-somnolence with compulsive eating or drinking and hypersexuality for several years. HLA-DR typing was HLA-DR3 and 13 in case 1 and HLA-DR4 and 10 in case 2. Case 1 showed hypersomnia with early onset of REM sleep on MSLT and frequent frontal intermittent rhythmic delta activity on EEG. Both cases showed no abnormalities on brain MRI. HLA-DR typing facilitates differentiation between KLS and narcolepsy by the absence of HLA-DR2.

Cytotoxic T Lymphocyte Antigen-4 (CTla-4) Polymorphism in Korean Autoimmune Thyroid Disease / 대한내분비학회지

BACKGROUND: The cause of autoimmune thyroid diseases (AITD), including Graves disease and Hashimotos thyroiditis, is largely unknown. To identify the genes responsible, most attention has been focussed on the HLA regions in the early studies. However, these studies have repeatedly shown a weak association between AITD and the HLA-DR3 in Caucasians. To understand and find out the mechanisms underlying the development of AITD, a search for non-HLA linked susceptibility genes is important. A recent study from American population have indicated an association between a polymorphism of CILA-4 gene and Graves disease. To clarify the relationship of the CTLA-4 polymorphism and AITD, the allele frequency of CTLA-4 gene from the patients with Graves disease and with Hashimotos thyroiditis in Korean papulation were analysed. METHODS: The CTLA-4 exon 1 polymorphism (49, A/G) was analysed by PCR-based, RFLP (Restriction Fragment Length Polymorphism) from 92 women and 37 men with Graves disease and 50 women and 9 men with Hashimotos thyroiditis diagnosed. Also, 287 healthy controls including 155 women and 132 men with no clinical evidence or family history of thyroid disease were enrolled. RESULTS: 1) In the group of Graves disease, there was significantly more patients with alanine homozygote (GG) than in control group (P<0.0005, RR=1.40). However, there was not significant with threonine homozygote (AA) between two groups (P=0.052). In the group of Hashimotos thyroiditis, no significant differences were found between all homozygotes and heterozygote. 2) In the group of Graves disease, there were significantly more patients with alanine homozygote (GG) (P<0.0001, RR=1.85) and significantly fewer patients with threonine homozygote (AA) than in the group of Hashimoto's thyroiditis (P<0.005, RR 0.25). CONCLUSION: Regardless of sex difference, alanine homozygote (GG) at exon 1 (codon 17) of CTLA-4 is associated with Graves disease in Korean population, which suggests genetic susceptibility is some role in the pathogenesis of Graves disease.

Human leucocyte antigen and insulin dependent diabetes mellitus.

HLA typing was done in 25 cases of insulin dependent diabetes mellitus (IDDM) and compared with 60 healthy controls. There was a significantly increased frequency of HLA B-8, HLA B-12 and HLA DR-3 in IDDMO. The odds ratio (relative risk) of developing IDDM for HLA B-8 was 4.42 (p less than 0.10), for HLA B-12 was 3.56 (p less than 0.10) and for HLA DR3 9.75 (p less than 0.001). There was no correlation of HLA specificity with complications of diabetes.