Ganglionic acetylcholine receptor autoantibodies in patients with autoimmune diseases including primary biliary cirrhosis

Objectives: Autonomic dysfunction is closely associated with autoimmune diseases (AID) including primary biliary cirrhosis (PBC). The objective of this study was to determine the prevalence of anti-ganglionic (nicotinic) acetylcholine receptor (gAChR) antibodies in patients with AID.

Methods: We determined the presence of gAChR antibodies in serum samples from 146 patients (systemic lupus erythematosus [SLE]?=?32; rheumatoid arthritis [RA]?=?43; systemic sclerosis [SSc]?=?38; PBC=?33) without information regarding autonomic symptoms, as well as 34 patients with other neurological diseases [OND], and 73 healthy controls [HC]. We specifically analyzed sera for anti-gAChRα3 and -β4 antibodies using the luciferase immunoprecipitation system (LIPS) assay.

Results: LIPS assay detected anti-gAChRα3 and -β4 antibodies in the sera from patients with SLE (12.5%, 4/32), RA (18.6%, 8/43), SSc (13.2%, 5/38), PBC (9.1%, 3/33), OND (2.9%, 1/34), and HC (0.0%, 1/73). There were no significant correlations between the levels of anti-gAChRα3 and -β4 antibodies, and the total titers of autoantibodies in AID.

Conclusions: The results demonstrated a significant prevalence of anti-gAChR antibodies in patients with AID, which is independent of the production of other autoantibodies in patients with autoimmune diseases. These anti-gAChR antibodies could mediate the autonomic dysfunction involved in the autoimmune mechanisms of AID.     

The occurrence of systemic lupus erythematosus in an asymptomatic carrier of human T-cell lymphotropic virus type I

A 63-year-old asymptomatic carrier of human T-cell lymphotropic virus type I (HTLV-1) infection was admitted because of chest oppression, a high-grade fever, polyarthralgia, and erythematous rashes. Laboratory examination revealed lymphocytopenia, proteinuria, and high titers of antinuclear antibodies and antidouble-stranded DNA antibody; thus, she was diagnosed as having systemic lupus erythematosus (SLE). This case indicates that HTLV-1 infection might be related with the pathogenesis of SLE.     

自身免疫性肝炎和原发性胆汁性肝硬化患者自身免疫性甲状腺疾病流行率调查*

目的 调查自身免疫性肝病(AILD)患者自身免疫性甲状腺疾病(AITD)发病率情况。 方法 2018年6月～2020年12月我院诊治的自身免疫性肝炎(AIH)41例和原发性胆汁性肝硬化(PBC)患者45例,采用间接免疫荧光法或免疫印迹法检测血清抗核抗体(ANA)、抗线粒体抗体(AMA)或AMA-M2)、抗平滑肌抗体(ASMA)、抗双链DNA抗体(抗dsDNA)和抗着丝点抗体(ACA);采用ELISA法检测血清免疫球蛋白,包括IgG、IgM和γ-球蛋白。结果 在本组41例AIH患者中,合并HT患者12例,合并GD患者6例,在45例PBC患者中,合并HT患者8例,合并GD患者7例;AIH患者血清IgG水平为17.5(14.8,19.8)g/L,显著低于AIH合并HT组【21.6(17.5,29.0)g/L,P<0.05】或AIH合并GD组【22.4(20.2,26.4)g/L,P<0.05】,血清γ-球蛋白为22.2(19.3,25.6)%,显著低于合并HT组【26.5(22.2,32.2)%,P<0.05】或合并GD组【27.1(24.3,32.0)%,P<0.05】;PBC患者年龄为(55.2±1.1)岁,显著小于合并HT组【(62.4±1.6)岁,P<0.05】或合并GD组【(62.2±1.5)岁,P<0.05】,血清IgG水平为15.4(12.2,18.0)g/L,显著低于合并HT组【20.3(16.8,24.7)g/L,P<0.05】或合并GD组【21.3(16.8,25.6)g/L,P<0.05】,血清γ-球蛋白水平为21.2(17.8,25.6)%,显著低于合并HT组【26.7(21.7,30.4)%,P<0.05】或合并GD组【25.4(22.2,29.4)%,P<0.05】。结论 AILD合并AITD的发病率较高,合并AITD患者血清IgG和γ-球蛋白水平较高,其原因还有待于进一步研究。     

Abnormal galactosylation of serum IgG in patients with systemic lupus erythematosus and members of families with high frequency of autoimmune diseases

Summary Gas chromatographic carbohydrate analyses of IgG from 30 patients with idiopathic systemic lupus erythematosus (SLE) revealed lower content of galactose when compared to that in 36 controls of similar ages (mean ±SD, 3.18±0.66 vs 3.82±0.41 galactose residues/mole of IgG, P<0.001). Abnormal galactosylation was observed in 60% of SLE patients. Analyses of IgG from 58 members of five families, characterized by a high frequency of SLE and other autoimmune diseases and serological abnormalities, and 51 controls of similar age range revealed that IgG galactose deficiency was detecable not only in some members with clinical and serological abnormalities (P0.001), but also in those without evidence of autoimmune diseases or abnormal serologies (P0.001). These data indicate that abnormal galactosylation of IgG frequently occurs in asymptomatic members of families with a high frequency of SLE and other autoimmune diseases and suggests that this abnormality may be an indicator for the development of these diseases.     

Lupus erythematosus tumidus (LET) with autoimmune thyroid dysfunction (AITD) as the first presentation of systemic lupus erythematosus: A case report and review of the literature

IntroductionLupus erythematosus tumidus (LET) is a rare cutaneous manifestation especially as a first presentation of systemic lupus erythematosus (SLE). Autoimmune thyroid dysfunction (AITD) may be associated with SLE but rarely at initial presentation, and its diagnosis may be delayed.Case reportA 29 year old male presented to Tishreen Hospital in Damascus with a three-year history of recurrent cellulitis-like lesions on the face, and more recently, he developed similar lesions on the trunk and the chest, in addition to the development of peripheral and scrotal edema, constipation, xeroderma, hair loss, musculoskeletal pain and depression. Laboratory investigations revealed: leukopenia, anaemia, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Immunological tests identified the positive anti-nuclear antibody (ANA), anti-double stranded DNA (anti-dsDNA), anti Ro/SSA, anti La/SSB antibodies. Additionally, there was consumed complement C3, elevated thyroid stimulating hormone (TSH), thyroid hormones decreased free T3 and T4 and anti-thyroid peroxidase (anti-TPO) antibody was positive. Skin biopsy from the cheek plaque suggested the presence of LET and revealed slight hyperkeratosis; actinic elastosis, telangiectasia and edema of the papillary dermis; deep dermis perivascular and periadnexal inflammatory infiltrates with karyorrhexis of the lymphocytes and dermis edema between strands of collagen. The patient fulfilled the SLE classification criteria and consequently, methylprednisolone, azathioprine, hydroxychloroquine, levothyroxine were introduced with dramatic improvement.ConclusionLET is a rare cutaneous lupus-specific lesion that may be associated with SLE. AITD, hypothyroidism in particular, could be an initial presentation of SLE. Increased awareness and early diagnosis of such clinical presentations may improve patient outcomes.     

Thymocytotoxic antibodies in patients with autoimmune hemolytic anemia systemic lupus erythematosus and lymphoproliferative diseases

Summary Cytotoxic antibodies against human thymocytes have been found in the sera from patients with AIHA (52%), active SLE (80%) or lymphoproliferative diseases (74%). Only 42% of thymocytotoxic sera were also reactive against mature T lymphocytes, whereas 70% of the sera containing antibodies against T lymphocytes were also thymocytotoxic. The thymocytotoxic antibodies could play a possible pathogenic role in the development of immunologic abnormalities in these diseases including autoantibody formation through loss of thymus dependent lymphocytes, as in the NZB animal model.Supported by grant from the Ministry of Education     

自身免疫性疾病患者血清抗弓形虫抗体调查

目的 了解自身免疫性疾病患者弓形虫感染情况,为后续有针对性地开展弓形虫病防治工作提供依据.方法 以237例自身免疫性疾病确诊患者作为调查对象,其中系统性红斑狼疮患者79例、类风湿性关节炎患者71例、炎症性肠病患者87例,以237例健康志愿者作为对照.采用酶联免疫吸附试验检测自身免疫性疾病患者和健康对照者血清抗弓形虫Ig...     

Factors associated with pain in individuals infected by human T-cell lymphotropic virus type 1 (HTLV-1)

Introduction

Despite the high prevalence of chronic pain in individuals infected with HTLV-1, predictive and protective factors for its development are still unclear.

Epigenetics in autoimmune diseases with focus on type 1 diabetes

Autoimmune diseases arise when the body mounts an immune response against ‘self’ cells and tissues causing inflammation and damage. It is commonly accepted that these diseases develop because of the interplay of genetic and environmental factors. Evidence for genetic factors includes the higher concordance of disease in monozygotic twins than in dizygotic twins. However, monozygotic twins may remain discordant for disease indicating a role for environmental factors. Environmental factors may alter gene expression via epigenetic mechanisms. This is particularly pertinent in type 1 diabetes in which DNA methylation and histone modifications have been associated with altered gene expression. The low disease concordance rate in adult‐onset type 1 diabetes (<20%) suggests that environmental and epigenetic changes may play a predominant role. Defining the role of epigenetic changes could identify specific gene pathways and dysregulated expression of gene products that contribute to the pathogenesis of type 1 diabetes. This article reviews how epigenetic mechanisms may contribute to the development of autoimmune diseases with a focus on type 1 diabetes. Copyright © 2012 John Wiley & Sons, Ltd.     

肿瘤坏死因子α基因多态性与中国人自身免疫肝病相关性研究

目的 探讨肿瘤坏死因子α(TNFα)启动子基因多态性与中国人自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)发病的相关性。方法 采用序列特异性聚合酶链式反应方法分析49例AIH、58例PBC患者外周血单核细胞基因组DNA TNFα启动子308、-238G／A基因多态性，并与160例正常对照组比较。结果 正常对照组中国人与白种人TNFα*2携带率差异较大。虽然从百分率上可以看出中国人PBC患者TNFα*2携带率低于正常对照组(10．34％与16.88％)，但统计学上两者差异无显著性，TNFα-238位基因多态性分布也与正常对照组差异无显著性；AIH患者TNFα启动子-308、-238G／A基因多态性均与正常人差异无显著性。结论 不同人种自身免疫肝病的免疫相关基因不同，中国人AIH、PBC与TNFα启动子基因的多态性间不存在基因连锁关系。     

Thyroid dysfunction in patients with systemic lupus erythematosus (SLE): relation to disease activity

We examined the prevalence of thyroid dysfunction and the production of anti-thyroid antibodies (ATA) in patients with systemic lupus erythematosus (SLE) and assessed the association between ATA production and SLE disease activity status. Seventy-seven patients who met the American College of Rheumatology classification criteria for SLE participated in the study. Fifty-two individuals served as a control group. Demographic, clinical information and SLE disease activity (SLEDAI) status were collected from all patients. The sera of all participants were tested for free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroglobulin (ATg) and anti-thyroid peroxidase (TPO). A SLEDAI score of > or =6 was considered clinically significant. The results of the thyroid function tests and ATA were compared between the study group and the control group. ATA levels were compared between the patients with a SLEDAI score of > or =6 to those with a SLEDAI score of <6. Hypothyroidism was detected in 11.6% of SLE patients compared to 1.9% in the control group. None of the patients or controls had evidence of hyperthyroidism. No statistically significant difference was observed in the levels of ATg or TPO between the study group and the control group. No correlation was found between ATA levels and the degree of the disease activity. Among the different variables tested in this study, hypothyroidism was the only significant abnormal finding in SLE patients. No association was found between the SLEDAI score and the prevalence of ATA production. Larger controlled, longitudinal studies are necessary to confirm these findings and elucidate the role played by ATA in the pathogenesis of thyroid dysfunction in SLE patients.     

A human T-cell lymphotropic virus type 1 carrier presenting with Sj?gren's syndrome and bronchopneumopathy]

A 77-year-old asymptomatic woman was found to have a coin lesion on a chest radiograph. Chest computed tomography scans showed the coin lesion, bronchiectasis, tree-in-bud appearance, and ground glass opacity. The histopathology of the lung by video-assisted thoracic surgery showed organizing pneumonia, follicular bronchiolitis, and non-specific interstitial pneumonitis patterns, all of which consisted of mainly mature lymphocytes and plasma cells. She suffered from dry eyes and had a high level of serum anti-SS-A antibody. Examination of her eyes and mouth revealed Sj?gren's syndrome. The patient herself and her parents were born in Nagasaki prefecture, an area where human T-cell lymphotropic virus type 1 (HTLV-1) is endemic, and her sister suffered from a hematological malignancy. She was found to be an HTLV-1 carrier. We finally made a diagnosis of an HTLV-1 carrier presenting with Sj?gren's syndrome and bronchopneumopathy. This combination (HTLV-1, Sj?gren's syndrome, and bronchopneumopathy) is rarely reported.     

Autoantibodies against C-reactive protein (CRP) in sera of patients with systemic rheumatic diseases

Abstract

An assessment of the frequency of serum autoantibodies against modified C-reactive protein (mCRP) in systemic rheumatic diseases and the association of these autoantibodies with clinical and laboratory findings in patients with systemic lupus erythematosus (SLE). Serum levels of autoantibodies against mCRP were measured by an enzyme-linked immunosorbent assay in 125 patients with SLE and in 213 patients with other systemic rheumatic diseases. The frequency of patients with high antimodified CRP antibody levels was 32% in SLE, 22% in systemic sclerosis (SSc), 19% in polymyositis/dermatomyositis (PM/DM), 43% in primary Sjögren's syndrome (pSS), 29% in rheumatoid arthritis (RA), 33% in mixed connective tissue disease (MCTD), and 43% in overlap syndrome. Serum levels of anti-mCRP antibody were significantly lower in SLE patients with persistent proteinuria (P < 0.001), cellular casts (P < 0.01), and hypoalbuminemia (P < 0.05). Serum anti-mCRP antibody levels in SLE showed a direct correlation with serum IgG levels (P < 0.001), serum anti-SS-A antibody levels (P < 0.01), serum anti-SS-B antibody levels (P < 0.01), and serum anti-U1-RNP antibody levels (P < 0.05). Inhibition experiments revealed that nonnative epitopes on the CRP molecule, termed mCRP, were the main target of the anti-mCRP antibodies detected. Autoantibodies against mCRP were frequently found in sera from patients with systemic rheumatic diseases, and may have a role in the immunopathogenesis of systemic rheumatic diseases, which are characterized by persistent inflammation.     

Autoantibodies against C-reactive protein (CRP) in sera of patients with systemic rheumatic diseases

An assessment of the frequency of serum autoantibodies against modified C-reactive protein (mCRP) in systemic rheumatic diseases and the association of these autoantibodies with clinical and laboratory findings in patients with systemic lupus erythematosus (SLE). Serum levels of autoantibodies against mCRP were measured by an enzyme-linked immunosorbent assay in 125 patients with SLE and in 213 patients with other systemic rheumatic diseases. The frequency of patients with high antimodified CRP antibody levels was 32% in SLE, 22% in systemic sclerosis (SSc), 19% in polymyositis/dermatomyositis (PM/DM), 43% in primary Sjögren's syndrome (pSS), 29% in rheumatoid arthritis (RA), 33% in mixed connective tissue disease (MCTD), and 43% in overlap syndrome. Serum levels of anti-mCRP antibody were significantly lower in SLE patients with persistent proteinuria (P < 0.001), cellular casts (P < 0.01), and hypoalbuminemia (P < 0.05). Serum anti-mCRP antibody levels in SLE showed a direct correlation with serum IgG levels (P < 0.001), serum anti-SS-A antibody levels (P < 0.01), serum anti-SS-B antibody levels (P < 0.01), and serum anti-U1-RNP antibody levels (P < 0.05). Inhibition experiments revealed that nonnative epitopes on the CRP molecule, termed mCRP, were the main target of the anti-mCRP antibodies detected. Autoantibodies against mCRP were frequently found in sera from patients with systemic rheumatic diseases, and may have a role in the immunopathogenesis of systemic rheumatic diseases, which are characterized by persistent inflammation.     

Human T-cell lymphotropic virus type 1 (HTLV-1) and lymphoid malignancies in Dominica: a seroprevalence study

Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in certain regions of the world where it is associated with lymphoid malignancies. Herein we aim to describe the seroprevalence of HTLV-1 in lymphoid malignancies in Dominica. We carried out a 10-year retrospective study of histologically proven hematologic malignancies and HTLV-1 seropositivity at the Princess Margaret Hospital, Dominica. Ninety-eight cases were reviewed (59% males, 41% females), ranging in age from 3 to 91 years. HTLV-1 was seropositive in 38.6% (31/80) of all hematologic malignancies. Three of 6 cases of Hodgkin disease (50%), 16 of 36 (44.4%) of non-Hodgkin lymphoma, and 3 out of 8 unclassified lymphomas (37.5%) were seropositive; all 6 cases (100%) of acute adult T-cell leukemia/lymphoma (ATLL) were seropositive. One case each of chronic lymphocytic leukemia and myeloproliferative disorder was seropositive. HTLV-1-seropositive lymphomas presented at a younger age than did seronegative cases. Thus, HTLV-1 is significantly associated with lymphoid malignancies in Dominica, and further studies are needed before a causal relationship with Hodgkin disease can be established.