Distinctive autoantibody profile in Mexican Mestizo systemic sclerosis patients

Systemic sclerosis (SSc) shows variable clinical expression among different ethnic groups. Herein, we describe the clinical features, prevalence of organ involvement, and autoantibody profile in Mexican Mestizo SSc patients and we compare them with patients from other ethnic groups.We included 139 SSc patients. They underwent clinical evaluation and were tested for antinuclear antibodies (ANA), anticentromere antibodies (ACA), anti-topoisomerase I, anti-RNA polymerase III, anti-U1 RNP, anti-U3 RNP, anti-U11/U12 RNP, anti-Th/To, anti-PM-Scl, anti-Ku, antinucleosome, anti-double-stranded DNA (dsDNA), anti-Sm, anti-SSA, and anti-SSB antibodies. Female predominance (93.5%) was noted; 56.8% of patients had limited cutaneous SSc; 91% had peripheral vascular involvement; 70% had joint involvement; 27% had musculoskeletal damage; 66% had gastrointestinal involvement; 41% had interstitial lung disease; 32% had pulmonary arterial hypertension (PAH); 11% had cardiac involvement; and in 1.4% renal involvement was observed. Our patients showed lower frequency of renal crisis and higher frequency of PAH than patients from other ethnic groups; also they showed higher frequency of ACA than Japanese and African American patients, higher frequency of anti-topoisomerase I than Caucasian and African American patients, higher frequency of anti-PM-Scl and anti-Ku and lower frequency of anti-RNA Pol III than the other ethnic groups. High frequencies of antinucleosome (41%) and anti-dsDNA (63%) were identified. SSc-specific autoantibody frequencies are different in our patients and in those from other ethnic groups; associations of autoantibodies with clinical manifestations are confirmed in our patients. Ethnicity and the interaction of gene and environmental factors may influence the clinical picture and autoantibody profile in SSc patients.     

Disease-related autoantibody profile in patients with systemic sclerosis

Background: Autoantibodies (autoAbs) help in diagnosis and predicting clinical phenotypes in systemic sclerosis (SSc).

Aim of the study: To determine the clinical utility of 13 SSc-related autoAbs in SSc patients.

Material and methods: A total of 131 consecutive patients with SSc (111 female, mean age 58.1?±?14 years; 49 with diffused cutaneous SSc [dcSSc] and 82 with limited cutaneous SSc [lcSSc]) were analysed by a multiplex line immunoassay (Euroimmun) for autoantibodies (autoAbs) against 13 SSc-related antigens. A total of 22 patients with primary Raynaud phenomenon (RP), and 22 healthy controls were also analysed.

Results: ANA by indirect immunofluorescence was present in 128 (97.7%) patients with SSc. Excluding anti-Ro52, 113 (89.3%) SSc patients were positive for at least one autoAb: anti-Topoisomerase I (anti-Topo) I abs in 54 (41.2%), anti-centromere proteins (anti-CENP) in 37 (28.2%, all reactive with centromere protein-A (CENPA) and centromere protein B (CENPB)), anti-RNA polymerase III(RP11) in 19 (14.5%), anti-RNA polymerase III(RP155) in 13 (9.9%), anti-fibrillarin in 4 (3.1%), anti-Ku in 6 (4.6%), anti-nucleolus-organizing region (anti-NOR90) in 8 (6.1%), anti-PM-Scl100 in 2 (1.5%), and anti-PM-Scl75 in 4 (3.1%). There was no immunoreactivity for Th/To or platelet-derived growth factor receptor (PDGFR). Overall, 102 (77.9%) SSc patients had autoAbs against Topo I, CENPA or CENPB, RP11 or RP155. Anti-Topo I abs were strongly associated with dcSSc, interstitial lung disease (ILD) (p?p?=?.019) and ILD-PH (p?=?.003). Anti-CENPB abs were associated with lcSSc, and negatively associated with ILD. Anti-RP11 and anti-NOR90 abs were associated with male gender, and anti-NOR90 associated with ILD.

Conclusions: Anti-Topo I, anti-CENP, and anti-RNA pol III are the most prevalent autoAbs in SSc. Anti-Topo I and anti-NOR90 abs are associated with ILD and/or PAH.     

Decreased levels of autoantibody against histone deacetylase 3 in patients with systemic sclerosis

Systemic sclerosis (SSc) is characterized by immunological abnormalities, especially the production of autoantibodies against various cellular components. Treatment with histone deacetylase (HDAC) inhibitors prevents collagen accumulation in a mouse SSc model. Additionally, autoantibody against HDAC-3 is produced in colon cancer patients, while HDAC-1 and HDAC-2 do not elicit autoantibody response. To determine the presence and levels of antibodies (Abs) against HDAC-3 in SSc. Anti-HDAC-3 Ab was examined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting using human recombinant HDAC-3. The HDAC-3 activity was evaluated by ELISA using the fluorimetric HDAC lysyl substrate that comprises an acetylated lysine side chain. Contrary to our hypothesis that autoimmune background in SSc induced the production of autoantibody against HDACs, IgG and IgM anti-HDAC-3 Ab levels in SSc patients were significantly lower than in normal controls (p < 0.0005 and 0.001, respectively). Furthermore, decreased levels of IgG anti-HDAC-3 Ab were specific to SSc, since IgG anti-HDAC-3 Ab levels in patients with dermatomyositis (DM) and those with systemic lupus erythematosus (SLE) were similar and slightly increased relative to normal controls, respectively. Immunoblotting analysis showed that anti-HDAC-3 Ab was detected in normal controls and patients with DM or SLE, while it was absent in SSc patients. The HDAC-3 activity was significantly inhibited by IgG isolated from sera of normal controls, whereas such inhibitory effect was not observed by IgG isolated from sera of SSc patients. These results indicate the lack of anti-HDAC-3 autoantibody in SSc patients, which is produced in healthy individuals as well as DM and SLE patients, suggesting that this autoantibody might function as protective Ab.     

Anti-collagen antibodies in systemic sclerosis and in primary Raynaud's phenomenon.

The frequency and specificity of antibodies to native and denatured collagens were evaluated in systemic sclerosis (SSc) and in primary Raynaud's phenomenon (PRP) by direct and competitive ELISA. Antibodies reactive with denatured collagen type I (CI) were found in 43% of the SSc sera, and anti-CIV and anti-CV in 31%. In PRP, anti-CI, anti-CIV and anti-CV antibodies were detected in 8% of patient sera. Anti-CI, anti-CIV and anti-CV antibodies reacted with determinants expressed on the native as well as on the denatured molecule. Anti-CI and anti-CIV were cross-reactive; a reactivity with CII and a lower one with CV were detected. Anti-CV antibodies also reacted with CI and CII and, in a smaller proportion of cases, with CIV. Anti-collagen antibodies, affinity-purified from blotted collagen IV and V and cyanogen bromide (CBr)-digested CI, displayed the cross-reactivities shown by inhibition studies on sera. Moreover, antibodies eluted from a CBr fragment of CI reacted with the other CBr fragments as well. These data show that one-third of SSc sera contain antibodies that react with epitopes expressed on native as well as on heat-denatured CI, CII, CIV and CV, and therefore have the potential to bind collagens in vivo.     

Recent advances in understanding the clinical utility and underlying cause of antinucleosome (antichromatin) autoantibodies

The clinical utility of measuring antinucleosome autoantibodies (also known as antichromatin) in patients with systemic lupus erythematosus (SLE) has recently been evaluated by a number of different groups. Many studies found that antinucleosome autoantibodies were more prevalent than anti-DNA in SLE patients. In addition, antinucleosome autoantibodies were usually found to correlate with glomerulonephritis or disease activity better than anti-DNA in these patients. Antinucleosome autoantibodies are also found in patients with drug-induced lupus and Type I autoimmune hepatitis, but not usually in other diseases, thus showing good specificity for the above diseases. Several studies have shown that individuals with SLE have T cells reactive with nucleosomes and have increased levels of nucleosomes in their sera. The antinucleosome response in murine models of SLE is also T-cell-dependent and appears to be driven by self antigen. Nucleosome-antinucleosome immune complexes bind to glomeruli in vitro, and antinucleosome autoantibodies have been eluted from the kidneys of people and mice with glomerulonephritis. In one strain of mouse it was shown that antinucleosome autoantibodies were necessary, but not sufficient, to cause glomerulonephritis. These findings all show that antinucleosome autoantibodies are a sensitive and specific diagnostic marker for SLE and contribute to the pathology of glomerulonephritis.     

Proximal interleukin-10 gene polymorphisms in Italian patients with systemic sclerosis

Interleukin-10 (IL-10) can favour the development of fibrosis by promoting a relative shift towards T helper 2 responses. Three single base pair substitutions in the 5' flanking region of the IL-10 gene (G/A -1082, C/T -819 and C/A -592) influence the amount of IL-10 secreted in cell cultures: the GCC haplotype is associated with an increased production, while the ACC and the ATA haplotypes are associated with intermediate and decreased production. Accordingly, three phenotypes have been individuated: high producers (GCC+/GCC+), medium producers (GCC+/GCC-) and low producers (GCC-/GCC-). We hypothesised that IL-10 haplotypes and genotypes are differently expressed in patients with systemic sclerosis (SSc) with the limited cutaneous SSc (lcSSc) subset or the diffuse cutaneous SSc (dcSSc) subset. One hundred and sixty-one unrelated Italian patients with SSc and 94 controls have been included. Their DNA was extracted and stored before being analysed by polymerase chain reaction with sequence-specific primers. The GCC haplotype is overrepresented in patients with SSc; subjects with dcSSc were the primary contributors to these results (dcSSc: 52.2% vs controls: 37.2%; chi2= 8.519, 2 d.f., corrected P= 0.04). In Scl70-positive patients, the GCC haplotype increased the likelihood of presenting the dcSSc subset [chi2= 12.56, P < 0.0005; odds ratio (OR) = 3.89, 95% confidence interval (CI(95)) = 1.69-9.08]; these results were confirmed at the phenotypic level (chi2= 11.67, 2 d.f., P= 0.003). In Scl70-positive patients, the high-producing phenotype was associated with poor survival, independently from disease subset and gender (hazard ratio = 9.9, CI(95)= 1.6-61.27, P < 0.05). The IL-10 haplotype and genotype associated with high IL-10 production may alter the susceptibility to SSc and/or its expression, increasing the prognostic value of other well-known markers of disease severity.     

A recombinant topoisomerase I used for autoantibody detection in sera from patients with systemic sclerosis.

We reported three additional cases of a newly described syndrome called episodic angioedema with hypereosinophilia. In order to investigate its pathophysiological mechanisms, four parameters were concurrently investigated, including blood eosinophil density, serum chemoattractant activity, serum major basic protein (MBP) levels and the presence of anti-endothelial cell antibodies. Distribution of eosinophils through a metrizamide density gradient showed a preferential sedimentation of blood eosinophils in intermediate layers, clearly different from the hypodense cells (low-density layers) identified in a group of seven patients with idiopathic hypereosinophilic syndrome (HES). In two of the three patients with cyclic angioedema, a chemotactic activity towards eosinophils was detected in the serum (30 +/- 6 and 42 +/- 12 eosinophils per high-power field; P less than 0.05 compared with a control group). Serum MBP levels were at 1524, 619 and 1200 pg/ml. All three patients had circulating anti-endothelial cell antibodies, predominantly of the IgG isotype, in contrast to controls (P less than 0.01) or to patients with HES (P less than 0.01). Specificity of the antibody for endothelial cells was demonstrated in the three patients studied by the absence of binding to various blood cells, including monocytes, lymphocytes, eosinophils and platelets. In one case (patient 2), the levels of anti-endothelial cell antibodies, as well as the serum chemoattractant activity to eosinophils varied according to the successive acute phases of the disease. Although further investigations are needed to clarify the exact pathophysiology of this syndrome, and especially the possible participation of the anti-endothelial cell antibodies in the cutaneous lesions, these data suggest that angioedema observed in this syndrome could result from the combined effects of activated eosinophils and of immunologically induced endothelial lesions.     

Ocular findings in patients with systemic sclerosis

OBJECTIVE:

To evaluate the frequency and characteristics of ocular manifestations in outpatients with systemic sclerosis.

METHODS:

In this cross-sectional study, 45 patients with systemic sclerosis were enrolled. Data regarding demographics, disease duration and subtype, age at diagnosis, nailfold capillaroscopic pattern and autoantibody profile were collected, and a full ophthalmic examination was conducted. Parametric (Student''s t-test) and nonparametric (Mann-Whitney U test) tests were used to compare continuous variables. Fisher''s exact test was used to compare categorical data. P values < 0.05 were considered significant.

RESULTS:

Twenty-three subjects (51.1%) had eyelid skin changes; 22 (48.9%) had keratoconjunctivitis sicca, 19 (42.2%) had cataracts, 13 (28.9%) had retinal microvascular abnormalities and 6 (13.3%) had glaucoma. Eyelid skin changes were more frequent in patients with the diffuse subtype of systemic sclerosis and were associated with a younger age and an earlier age at diagnosis. Cataracts were presumed to be age-related and secondary to corticosteroid treatment. There was no association between demographic, clinical or serological data and keratoconjunctivitis sicca. The retinal microvascular abnormalities were indistinguishable from those related to systemic hypertension and were associated with an older age and a severe capillaroscopic pattern.

CONCLUSIONS:

Eyelid skin abnormalities and keratoconjunctivitis sicca were the most common ocular findings related to systemic sclerosis. Some demographic and clinical data were associated with some ophthalmic features and not with others, showing that the ocular manifestations of systemic sclerosis are characterized by heterogeneity and reflect the differences in the implicated pathophysiological mechanisms.     

T lymphocyte abnormalities in juvenile systemic sclerosis patients

Multi-center evaluations of pediatric patients with juvenile systemic sclerosis (jSSc) have suggested that the pathogenesis of jSSc may differ from that of systemic sclerosis (SSc) in adult patients. Therefore, we undertook to identify abnormalities in the T lymphocytes of jSSc patients and to determine if they differed from the abnormalities reported in the T lymphocytes of adult SSc patients. We identified decreases in the frequency of resting regulatory T lymphocytes and an increased frequency of CD45RA expressing effector memory (EMRA) CD4 T lymphocytes, which were characterized by an increased frequency of CCR7 protein expressing cells. Neither the increases in the EMRA subpopulation nor the increased CCR7 protein expression have been reported in adult SSc patients. The decrease in resting regulatory T lymphocytes in jSSc patients may permit the expansion of the disease initiating CD4 T lymphocytes present in the CCR7 expressing EMRA CD4 T lymphocyte subpopulation.     

Measuring and managing appearance anxiety in patients with systemic sclerosis

Introduction: Systemic sclerosis (SSc, scleroderma) is a progressive, autoimmune, connective tissue disease of unknown etiology that can cause changes in appearance in socially important areas of the body (e.g. face and hands). Social concerns related to changes in appearance can contribute to anxiety specific to situations where one’s appearance will be evaluated, or appearance anxiety. Appearance anxiety is a relevant but underexplored construct in SSc.

Areas covered: We review the current knowledge on appearance anxiety in SSc, including assessment of the construct and interventions. Relevant references in the field were obtained through a literature search in MEDLINE/PubMed and PsycINFO for articles published through September 2018.

Expert commentary: There is a dearth of research in the SSc literature examining the construct of appearance anxiety. A growing interest in appearance anxiety in SSc has led to several relevant measures being validated in this population, including the Social Appearance Anxiety Scale. Important areas for future research are the development of interventions to address appearance anxiety and the use of randomized controlled trials to evaluate these interventions.     

Transforming growth factor-beta1 polymorphisms in Korean patients with systemic sclerosis

Transforming growth factor-beta1 (TGF-beta1) plays an important role in the pathogenesis of systemic sclerosis (SSc). To investigate the role of TGF-beta1 gene polymorphisms in SSc, we genotyped six biallelic polymorphic positions (position -988, -800, and -509; and codons 10, 25, and 263) in 61 Korean SSc patients and in 148 healthy controls, using polymerase chain reaction-sequence-specific primers. Genetic polymorphisms were found at position -509 and codon 10 in Koreans. The allele frequencies of C/T at position -509 were 0.59/0.41 in patients and 0.56/0.44 in controls. The allele frequencies of C/T at codon 10 were 0.40/0.60 in patients and 0.50/0.50 in controls. In conclusion, no skewed distribution of TGF-beta1 gene polymorphisms was found in Korean patients with SSc.     

Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis

Systemic sclerosis (SSc) is characterized by multi-organ fibrosis with an autoimmune background. Although autoantibodies are detected frequently in SSc patients, the role of autoantibody in the development of fibrosis remains unknown. Connective tissue homeostasis is a balance between the synthesis and degradation of the extracellular matrix (ECM); ECM degradation is regulated mainly by matrix metalloproteinases (MMPs). Anti-MMP-1 antibody is suggested to inhibit MMP-1 and be involved in the development of the fibrosis in SSc. However, the accumulation of various ECM components in the tissue of SSc cannot be explained by the anti-MMP-1 antibody alone. In this study, we examined the presence or levels of antibody to MMP-3, a protein which degrades various ECM components relevant to SSc fibrosis. Enzyme-linked immunosorbent assay (ELISA) using human recombinant MMP-3 revealed that IgG anti-MMP-3 autoantibody levels were elevated significantly in the sera from SSc patients, but not in patients with active systemic lupus erythematosus or dermatomyositis. IgG and IgM anti-MMP-3 antibody levels were significantly higher in diffuse cutaneous SSc, a severe form, than those in limited cutaneous SSc. Consistently, IgG anti-MMP-3 antibody levels correlated significantly with fibrosis of the skin, lung and renal blood vessels. The presence of IgG anti-MMP-3 autoantibody in sera from SSc patients was confirmed by immunoblotting analysis. Remarkably, MMP-3 activity was inhibited by IgG anti-MMP-3 antibody. These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM turnover.     

博来霉素诱导的硬皮病小鼠研究进展

硬皮病是一种以纤维化为主要病变的结缔组织病,其发病机制尚不清楚,临床缺乏有效治疗,迫切需要建立合适的动物模型对之展开研究.本文简述了博来霉素诱导的硬皮病小鼠模型的建立方法,并对其在发病机制和治疗学方面的研究作了归纳.     

Impairment of the inhibitory effect of sodium on basophil histamine release in patients with systemic sclerosis

It has been demonstrated that Na⁺ down-regulates IgE-dependent and IgE-independent histamine release from basophils of normal subjects. The aim of this study was to evaluate whether Na⁺ exerts its inhibitory effect on basophil histamine release in patients with systemic sclerosis (SSc). Peripheral blood leucocytes were stimulated with anti-IgE, n-formyl-methionyl-leucyl-phenylalanine (fMLP) and IL-3 in the presence of high and low Na⁺ concentrations, and histamine release was measured by a fluorometric method. The dose–response curves of histamine release induced by the above stimuli were similar in SSc patients (n = 15) and in normal subjects (n = 39). Na⁺ removal from the extracellular medium and its isosmotic replacement with choline chloride led to a significant increase of anti-IgE-and fMLP-induced histamine release in normal subjects, but not in SSc patients. In the former population, histamine release induced by an optimal dose of anti-IgE (1/5000) was 26.4 ± 3.1% in high Na⁺ and 59.3 ± 3.5% in low Na⁺ (mean ± s.e.m., P< 0.0001), whereas in the latter population mean histamine release was 20.4 ± 5.1% in high Na⁺ and 15.8 ± 2.9% in low Na⁺ (P NS). A similar trend was observed when basophils were stimulated with fMLP. Na⁺ exerted a dose-dependent inhibitory effect on anti-IgE- and fMLP-induced histamine release in normal subjects, but not in SSc patients. IL-3-induced histamine release from basophils of SSc patients was increased in a low-Na⁺ solution, but to a lesser extent when compared with normal controls. Therefore basophils from normal subjects and SSc patients behave in a different way when stimulated in a low-Na⁺ medium. The inhibitory effect of Na⁺ on basophil histamine release is impaired in SSc patients, and this abnormality could contribute to basophil dysfunction.     

Pamidronate infusion in patients with systemic sclerosis results in changes in blood mononuclear cell cytokine profiles

A single infusion of pamidronate was given to patients with systemic sclerosis (scleroderma, SSc) to assess effects on cytokine production by peripheral blood mononuclear cells (PBMC) and lymphocyte subsets. Eighteen patients with SSc received a single intravenous dose of 60 mg of pamidronate and were followed for 6 months. Assessment of cytokine production [interferon (IFN)-gamma, interleukin (IL)-10, transforming growth factor (TGF)-beta1, tumour necrosis factor (TNF)-alpha and IL-4] by PBMC and lymphocyte subsets by flow cytometry was carried out before and after the pamidronate infusion. Unstimulated PBMC produced increased amounts of IFN-gamma and TNF-alpha and reduced levels of TGF-beta1 for up to 24 weeks after the infusion. gammadelta T cells from patients with SSc were activated in vitro and produced increased IFN-gamma. The effects of pamidronate on modulation of cytokine profiles in patients with SSc may merit future study.     

Clinical and serological associations with anti-RNA polymerase antibodies in systemic sclerosis.

There are three classes of RNA polymerase enzyme (RNAPs I, II and III). In systemic sclerosis (SSc), three main groups of anti-RNAP sera have been characterized by radioimmunoprecipitation techniques: anti-RNAP I/III sera, anti-RNAP I/II/III sera, and a group precipitating both RNAP II and topoisomerase I (topo I). Some sera in this third group precipitate the phosphorylated (IIO) form of RNAP II in the absence of the unphosphorylated (IIA) form. Certain other antinuclear antibodies (ANA) have also been detected in anti-RNAP IIO/IIA/topo I and anti-RNAP IIO/topo I sera. In the present study of 155 SSc patients, clinical features of individuals from each of these antibody groups were assessed and compared with those of patients from other autoantibody-defined groups. The anti-RNAP I/II/III antibody specificity was closely associated with the presence of diffuse cutaneous SSc (dc-SSc) (77.8%; cf. remaining group, 12.4%; P < 0.001; relative risk (RR) 6.3). Patients with anti-RNAP I/III antibodies also had an increased incidence of dc-SSc, but this was not significant (42.9%; cf. remainder, 15.7%). Anti-RNAP+ patients had a significantly increased incidence of renal involvement (29.0%, cf. remainder, 11.3%; P < 0.05; RR 2.6), with 40% of anti-RNAP I/II/III patients having renal disease. Meanwhile, the presence of anti-centromere antibodies (ACA) was associated with limited cutaneous SSc (lc-SSc) (100.0%; cf. remainder, 75.3%; P < 0. 005), together with reduced incidences of both renal disease (2.4%, cf. remainder, 22.1%: P < 0.01) and pulmonary fibrosis (21.4%, cf. remainder, 52.3%; P < 0.005; RR 1.9). Anti-topo I antibodies were associated with the presence of pulmonary fibrosis (69.7%; cf. remainder, 32.6%; P < 0.001; RR 2.1). A majority of anti-topo I sera were from lc-SSc patients, regardless of whether anti-topo I antibodies occurred alone (75.0%) or together with anti-RNAP IIO + IIA antibodies (75.0%), and this was similar to the remainder (86. 5%; NS). However, when anti-topo I+ patients were compared with the ACA group, and then with all anti-RNAP I+ patients (37.5% lc-SSc), significant differences were found in the occurrence of dc- versus lc-SSc (P < 0.005 and P < 0.05, respectively). In conclusion, these results confirm that there are three main groups of SSc sera, each characterized by the presence of a mutually exclusive SSc-specific autoantibody (ACA, anti-topo I or anti-RNAP I), and distinguished by patterns of cutaneous involvement and specific clinical features. It appears that, in each of the three groups of SSc patients, distinct pathological processes are occurring, which are responsible for the characteristic symptoms, for the modification of particular autoantigens and, consequently, for the production of particular autoantibodies. Based on these data, together with our previous results, it is further hypothesized that anti-RNAP II antibodies may be produced in the context of two different immune response pathways.     

HLA Study on Two Mexican Mestizo Families with Autoimmune Thyroid Disease

Several studies have been done regarding the genetic susceptibility to autoimmune thyroid disease, particularly those related to the role of Major Histocompatibility Complex (MHC) genes in the etiology of the disease. In the present study, we report class I and class II MHC haplotypes in nine individuals affected by Hashimoto thyroiditis and Graves' disease who belong to two distinct Mexican families. In one of the families, Hashimoto thyroiditis was associated with the Human Leukocyte Antigen (HLA) HLA-DR3 allele whereas in the other family the disease was associated with homozygosity for the HLA-DR4 (DRB1*0407), HLA-DQ3 (DQB1*0302) haplotype. On the other hand, Graves' disease was found to be associated in one of the families with HLA-DR2 (DRB1*1501) and in the other with homozygosity for the HLA-DR7 (DRB*0701) and HLA-DQ2 (DQB1*0201) haplotype. These results confirm that in Mexicans as in other ethnic groups, genes located within the MHC region are related to the genetic susceptibility to develop autoimmune thyroid disease.     

Membranoproliferative glomerulonephritis in systemic sclerosis of childhood

Summary The renal lesions of a 5-year-old girl with progressive systemic sclerosis are described. The nephropathy was clinically characterised by moderate proteinuria, microscopic hematuria and transient hypertension. Light microscopy showed membranoproliferative glomerulonephritis of segmental character. On electron microscopy intramesangial, subendothelial and extramembranous glomerular deposits were observed. By immunofluorescence microscopy deposits of IgG, Clq, C₄, C₃, C₅, C₈ und C₉ in a predominantly subendothelial location were found in all glomeruli. Vascular lesions were of minor degree. Histological and immunohistological findings are compatible with an immune complex disease.