Reactions to metals in patients with chronic fatigue and autoimmune endocrinopathy

Our study was designed to assess the effect of heavy metals on the severity of fatigue in autoimmune thyroid disease associated with autoantibodies against other endocrine organs. We compared our data with those obtained from other groups of patients. A total of five groups of patients were examined by their medical history, dental examination, and using a modified test of blast transformation of metals (Melisa): a) 10 fatigues female patients with autoimmune thyroidism and polyglandular activation of autoimmunity, b) 12 fatigued patients with autoimmune thyroidism, c) 28 fatigued patients free of endocrinopathy, d) 22 professionals without evidence of autoimmunity, e) 13 controls, a population sample, the individuals did not complain of marked fatigue and their laboratory tests did not show signs of autoimmunity and endocrinopathy. Fatigue regardless of the underlying disease is primarily associated with hypersensitivity to inorganic and organic mercury, nickel, and gold. The groups differed in their hypersensitivity to other metals. In the control group, hypersensitivity--mostly to cadmium and lead--was found in four of the examined individuals only. Statistical analysis of data obtained from professionals and controls revealed a higher incidence of positivity to organic and inorganic mercury and nickel in professionals.     

The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl.

The clinical and laboratory features of 32 patients with anti-PM-Scl were studied. Patients with this rare autoantibody suffered from a homogenous overlap connective tissue disease defined by Raynaud phenomenon (32/32), features of scleroderma (31/32), arthritis (31/32, erosive in 9/32), myositis (28/32), lung restriction (25/32), calcinosis (15/32), and sicca (11/32). Significant renal and neurologic involvement was uncommon. All patients examined (22/22) had HLA-DR3, and 50% of these patients were homozygous. Our patients responded favorably to moderate immunosuppression and, with therapy, the disease generally has a good prognosis; over 50% of our series (17/32) remained well on minimal or no immunosuppression after a median follow-up of 8 years.     

A comparison of clinical and immunogenetic features in familial and sporadic rheumatoid arthritis

Clinical and immunogenetic factors were compared in 214 patients with sporadic rheumatoid arthritis (RA) and 117 patients from 52 multiplex families. Sex distribution, articular disease severity and seropositivity for rheumatoid and antinuclear factors were similar in familial and sporadic disease. There was a trend for Sj?gren's and Felty's syndromes to be more frequent in familial RA but extraarticular disease features were otherwise similar in the 2 RA disease groups. Mean age of onset was 41.1 years in familial and 46.5 years in sporadic RA (p less than 0.0006); 67% of family probands, 74% of affected relatives and 57% of sporadic patients were HLA-DR4 positive (p less than 0.05 affected relatives vs sporadic). The similarity of clinical features found in familial and sporadic RA justifies the use of families with RA to study aspects of disease pathogenesis.     

不同年龄组自身免疫性肝炎患者的临床特征分析

目的分析并比较不同年龄组自身免疫性肝炎（AIH）患者的临床特征、生化指标、免疫学指标和病理特点。方法 98例AIH患者按年龄分为青年（〈45岁）、中年（45～60岁）和老年（〉60岁）三组,回顾性比较三组患者临床特征、生化指标、免疫学指标、自身抗体和病理特点。结果老年组有并发症者显著高于青年组（50%vs 20%,P〈0.05）,其中,老年组肝硬化比例高于青年组（40.6%vs 5.7%,P〈0.05）。老年组TBil水平显著高于青年组,差异有统计学意义（P〈0.05）。中、老年组血清C4水平显著低于青年组（P〈0.05）;而lgG、lgM、lgA、C3水平差异无统计学意义。老年组抗核抗体（ANA）阳性率显著高于青年组（100%vs77.1%,P〈0.05）;青年组抗平滑肌抗体（SMA）阳性率显著高于老年组（31.4%vs 6.3%,P〈0.05）。中、老年组肝组织学界面炎比例显著高于青年组（88.5%、100%vs 51.8%,P〈0.05）;肝组织学炎症活动度评分（HAI）比较,中、老年组HAI高于靑年组差异有统计学意义（P〈0.05）。结论老年AIH患者在发病时肝硬化发生率高、肝病相关并发症比例高,肝脏炎症活动较重。     

Individual immunogenetic characterization of patients with diffuse toxic goiter and autoimmune thyroiditis

Statusmetry as a variant of a method of collective image recognition was used for evaluation of integral immunogenetic characterization of patients with toxic goiter (TG) and autoimmune thyroiditis (AT). Typing of 40 HLA antigens, class I, was performed in 114 TG patients, 106 AT patients and 500 healthy subjects, however this analysis employed the frequency of expression of 26 most informative specificities (9 alleles of locus A and 17 alleles of locus B of the HLA system). Functional models and decision rules to recognize TG, AT, remission and recurrence (decompensation) of TG were worked out. Recognition probability by the zero threshold was 68.4-78.3%. It was proposed that individual immunogenetic statusmetry should be used as part of diagnostic methods for TG and AT, their differential diagnosis, and a long-term prognosis of medicinal recurrence (decompensation) of TG.     

The clinical features of diabetes with coexisting autoimmune thyroid disease

Summary A study was made of the clinical features of diabetics with coexisting Graves' disease (n=117) or primary hypothyroidism (n=98). Those with Graves' disease developed thyroid dysfunction and diabetes at an earlier age than patients with primary hypothyroidism. There was, however, no difference between the two groups in respect of sex ratio nor proportion of subjects requiring insulin treatment. In contrast to the general diabetic population, 87% of diabetics with thyroid disease were female, 56% required insulin treatment and of patients requiring insulin from diagnosis, the median age at diagnosis of diabetes was 36 years. A strong correlation was observed between age at diagnosis of diabetes and that of hyperthyroidism (r=0.71, p< 0.001) or hypothyroidism (r=0.65, p<0.001). With increasing age at diagnosis of diabetes the interval between diagnosis of diabetes and thyroid disease diminished. The mean ± SEM interval between diagnosis of diabetes and that of thyroid dysfunction was longer in hypothyroid (6.7±1.2 years) than in hyperthyroid diabetics (-2.4 ±1.2 years). Neither insulin-dependent nor non-insulin dependent diabetics with associated thyroid disease exhibited a significant seasonal variation in diagnosis or symptomatic onset of diabetes. It is conceivable that where diabetes accompanies autoimmune thyroid disease in the same patient, both conditions may share a common and coincident pathogenesis which is unrelated to acute environmental influences.     

Polymyositis, dermatomyositis, and autoimmune necrotizing myopathy: clinical features

Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders predominantly affecting skeletal muscles, resulting in muscle inflammation and weakness. The 3 most common inflammatory myopathies are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. This review details the clinical findings noted in PM, DM, and the emerging entity of autoimmune necrotizing myopathy.     

Primary biliary cirrhosis: clinical and associated autoimmune features and natural history

Primary biliary cirrhosis, a chronic liver disease, predominately affects middle-aged women. The diagnosis is established by the presence of disease-specific autoantibodies and compatible liver histology showing focal immune-mediated damage to the intrahepatic bile ducts. Patients now are detected prior to the onset of symptoms typical of cholestasis with abnormal liver function tests, or even prior to the onset of abnormal liver function tests, with positive antimitochondrial antibodies. Earlier diagnosis is changing not only our appreciation of the prevalence of this condition, but also of the natural history. The disease appears to be heterogeneous with some patients having a slow progression and a normal life-expectancy, although other patients have a more aggressive course developing symptoms and end-stage disease that leads to death or liver transplantation.     

自身免疫病相关性胰腺炎的临床特点分析

目的 总结分析自身免疫病相关性胰腺炎的临床特点,提高对该类疾病的认识.方法 回顾总结北京协和医院诊断的28例自身免疫病相关性胰腺炎病例,结合伴发疾病分类分析.结果 (1)男女患者的比例为1:6,年龄(40.0±16.1)岁,自身免疫病相关性急性胰腺炎明显多于慢性胰腺炎(6:1);(2)常见的与胰腺炎相关的自身免疫病为系统性红斑狼疮(20/28)、干燥综合征(6/28)等;(3)与胰腺炎相关的自身免疫病的特点:有明显多系统受累表现,依次为血液系统、肾脏、肝脏等,胰腺炎发作出现于原发病的活动期;(4)自身免疫病相关性急性胰腺炎的临床特点:起病均无饮食诱因,影像学改变不明显;(5)自身免疫病相关性慢性胰腺炎的临床特点:可有CA199明显升高,但随病情好转而下降;(6)治疗与预后:加强的糖皮质激素或免疫抑制剂治疗有效,合并急性胰腺炎的患者的病死率较高(33.3%).结论 自身免疫病相火性胰腺炎以急性发病和女性患者多见,多与自身免疫病活动期相关,并发急件胰腺炎者预后差,糖皮质激素和(或)免疫抑制剂可缓解病情.     

The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations

Thirty-two patients with the Felty syndrome, defined by the presence of rheumatoid arthritis, splenomegaly, and neutropenia, have been studied in comparison with 32 patients with rheumatoid arthritis matched for age, sex, and disease duration, and 9 patients with rheumatoid arthritis and idiopathic neutropenia. Patients with the Felty syndrome had severe destructive arthritis, which progressed during follow-up despite little evidence of objective synovitis, and a higher frequency of extra-articular manifestations, including vasculitis. Bacterial infection tended to occur in patients with the lowest neutrophil count but continued to occur in some despite normalization of the WBC. Prognosis was poor and 8 deaths occurred, predominantly from sepsis. Serologic features were prominent. High titers of IgG rheumatoid factor and circulating immune complexes characterized patients with persistent neutropenia. A family history of rheumatoid arthritis was more common in patients with the Felty syndrome. The association with HLA DR4 was very strong; in addition there was an increased frequency of the DQw3 variant, 3b, suggesting that HLA Class II genes in linkage with DR4 may contribute to disease expression.     

Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase

OBJECTIVE: We have previously described anti-KS autoantibodies and provided evidence that they are directed against asparaginyl-transfer RNA (tRNA) synthetase (AsnRS). The aim of the present study was to identify patients with anti-AsnRS autoantibodies and elucidate the clinical significance of this sixth antisynthetase antibody. In particular, we studied whether it was associated with the syndrome of myositis (polymyositis or dermatomyositis [DM]), interstitial lung disease (ILD), arthritis, and other features that had been previously associated with the 5 other anti-aminoacyl-tRNA synthetase autoantibodies. METHODS: More than 2,500 sera from patients with connective tissue disease (including myositis and ILD) and controls were examined for anti-AsnRS autoantibodies by immunoprecipitation (IP). Positive and control sera were tested for the ability to inhibit AsnRS by preincubation of the enzyme source with the serum. The HLA class II (DRB1, DQA1, DQB1, DPB1) alleles were identified from restriction fragment length polymorphism of polymerase chain reaction-amplified genomic DNA. RESULTS: Anti-AsnRS antibodies were identified in the sera of 8 patients (5 Japanese, 1 American, 1 German, and 1 Korean) by IP of the same distinctive set of tRNA and protein that differed from those precipitated by the other 5 antisynthetases, and these antibodies showed specific inhibition of AsnRS activity. Two of these patients had DM, but 7 of 8 (88%) had ILD. Four patients (50%) had arthritis, and 1 had Raynaud's phenomenon. This antisynthetase was very rare among myositis patients (present in 0% of Japanese myositis patients), but it was found in 3% of Japanese ILD patients. Thus, most patients with anti-AsnRS had chronic ILD with or without features of connective tissue disease. Interestingly, all 4 Japanese patients tested had DR2 (DRB1*1501/1502), compared with 33% of healthy controls. CONCLUSION: These results indicate that anti-AsnRS autoantibodies, like anti-alanyl-tRNA synthetase autoantibodies, have a stronger association with ILD than with myositis and may be associated with the DR2 phenotype.     

Tiopronin-nephropathy: clinical, pathological, immunological and immunogenetic characteristics

Nine patients who developed proteinuria while on Tiopronin (a D-Penicillamine-like drug) have been studied. Nephrotic syndrome was observed in six cases. Immunologic analysis revealed a high frequency of ANA positivity and RF seronegativity by the time nephropathy appeared. Six patients were biopsied. Immunofluorescence, electron and light microscopy studies showed: glomerulonephritis with segmental deposits in the mesangium and along the capillary walls in one patient, mesangioprolipherative glomerulonephritis in one case and stage 1 membranous glomerulonephritis in four cases. Immunogenetic typing disclosed a strong association with B35-Cw4 class I antigens.     

The spondyloarthropathies in Zimbabwe: a clinical and immunogenetic profile

Spondyloarthropathies are rare in Africa and there is little data regarding HLA association. We prospectively studied 19 patients with spondyloarthropathy, recording clinical details and performing tissue typing (ABC loci). There were 9 patients with ankylosing spondylitis (8 males), all had severe spinal disease but none had ocular or cardiac involvement and HLA-B27 antigen was not found in any of the 7 patients tested; only one patient possessed a B7 crossreacting antigen. The 10 patients with Reiter's syndrome (8 males) had typical clinical features but again the HLA-B27 tissue type was not found. B7-CREG antigen was found in 7 of the 10 patients with Reiter's syndrome.     

190例自身免疫性肝病临床特征分析

目的 比较分析自身免疫性肝炎、原发性胆汁性肝硬化和重叠综合征的临床特征.方法 回顾性分析自身免疫性肝炎、原发性胆汁性肝硬化和重叠综合征患者的临床症状、体征、生化检查、免疫球蛋白、自身抗体、肝脏组织学等检查.结果 3组均以女性患者多见,以乏力、黄疸、瘙痒、脾大等为主要临床表现;3组患者白蛋白水平均下降,以原发性胆汁性肝硬化组下降最明显(P＜0.05);3组患者总胆红素、直接胆红素、丙氨酸氨基转移酶、天门冬氨酸氨基转氨酶、碱性磷酸酶和γ-谷酰转移酶均有升高,以重叠综合征升高最明显(P＜0.05).结论 自身免疫性肝病患者的临床特征可能对早期诊断有重要意义;肝功能总胆红素、直接胆红素、丙氨酸氨基转移酶、天门冬氨酸氨基转氨酶、碱性磷酸酶和T-谷酰转移酶等指标升高明显者需警惕重叠综合征的存在.     

以黄疸为首发表现的自身免疫性肝炎患者的临床特征

目的分析以黄疸为首发表现的自身免疫性肝炎(AIH)患者临床特点。方法选取AIH患者63例,其中以黄疸为首发表现的患者28例和非黄疸患者35例。比较两组患者临床症状体征、血清生物化学指标、免疫学指标及肝活组织病理。结果黄疸组与非黄疸组AIH患者相比,在免疫学指标、自身抗体阳性率、典型组织病理学特征比较,差异均无统计学意义(Z=-0.224、0.318,χ2=0.053、0.237、0.129、0.051,P均0.05),而黄疸组AIH患者的肝肾功能指标、肝组织炎症分级和纤维化分期、胆管反应发生率、肝小叶中央区坏死程度明显高于非黄疸组(χ2=12.504、0.026、0.009,Z=-2.213,P均0.05)。对本次试验中接受免疫抑制剂的AIH患者分别进行随访,达到生物化学缓解的患者有43例,用Kaplan-Meier法对生物化学缓解率进行分析,黄疸组患者的累积生物化学缓解率为80.5%,中位缓解时间为25个月(95%CI:22.921~29.349);非黄疸组患者的累积生物化学缓解率为93.2%,中位缓解时间为8个月(95%CI:4.150~9.940),差异具有统计学意义(χ2=7.139,P=0.008)。结论以黄疸为首发症状的急性AIH患者发生率较低,但肝组织损伤较为严重,治疗后缓解率较低。     

急性重症自身免疫性肝炎的临床特征和预后分析

目的:分析急性重症自身免疫性肝炎（AIH）的临床特征及预后。方法:回顾性分析2008-2019年入住空军军医大学第一附属医院的急性重症AIH患者临床资料,根据有无肝病基础分为急性AIH（A-AIH）和慢加急性AIH（AC-AIH）,分析患者一般情况、肝生物化学、免疫学、肝组织学特征、激素治疗预后及相关因素。结果:共收集...