Disturbed Complement Receptor Expression Pattern of B Cells Is Enhanced by Toll-like Receptor CD180 Ligation in Diffuse Cutaneous Systemic Sclerosis.

Autoantibody production is a hallmark of systemic sclerosis (SSc) and the most extensively studied role of B cells in the pathogenesis of the disease. However, the potential involvement of innate immune molecules in B-cell dysfunction in SSc is less understood. B-cell activation is an early event in the pathogenesis of SSc and is influenced by complement receptors (CRs) and Toll-like receptors (TLRs), shaping antibody responses. CR2 and CR1 modulate B-cell activation, and the roles of CR3 and CR4 are associated with autoimmune conditions. We investigated the expression of CRs in B cells from patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and the effect of TLR CD180 ligation on their expression. We found no significant difference in the basal expression of CD21 and CD11c in B cells between dcSSc and healthy controls (HCs). However, reduced basal CD11b expression in B cells in dcSSc compared to HCs, accompanied by a decrease in CD35 and an increase in CD11c expression following CD180 ligation may promote plasma cell formation and autoantibody production. Additionally, we searched for correlations between dcSSc-associated anti-DNA topoisomerase I (Scl-70) autoantibody, anti-citrate synthase (CS) natural autoantibody and complement component 3 (C3) levels and found a negative correlation between C3 and anti-CS autoantibody in dcSSc but not in HCs, supporting the hypothesis that natural autoantibodies could activate the complement system contributing to tissue injury in SSc.

Systemic sclerosis in mother and daughter with susceptible HLA haplotype and anti-topoisomerase I autoantibodies.

Systemic sclerosis is a rare systemic autoimmune rheumatic disease which is thought to be polygenic disorder contributed by both genetic and environmental factors. A positive family history of SSc is the strongest risk factor yet identified for SSc; however, the absolute risk for each family member remains quite low. A systematic literature search was performed in MEDLINE and Scopus database for studies published only in English that investigated the prevalence of SSc in first-degree relatives of SSc patients and whether SSc family members have greater frequency of I autoantibodies (ATA) than expected. Following keywords and terms: "systemic sclerosis", "scleroderma", "familial","ATA", "topoisomerase", and "anti-Scl70" were used to select the appropriate articles. From the 21 initially identified articles, 16 were eliminated because of the inclusion criteria, and five articles concerning familial occurrence of SSc in first-degree relatives positive for ATA were included for further analysis. Two case reports were described-a daughter and a mother diagnosed with systemic sclerosis with ATA tested for specific genotype. In both cases, patients had antinuclear autoantibodies (ANA) at a titer of > 1:1280, AC-29 cell pattern according to ICAP, and their sera were positive for ATA. In addition, anti-SSA/Ro60 autoantibodies were found in the case of the mother. Complementary to ATA positivity, the daughter was also positive for AMA-M2 autoantibodies. The results showed that our patients shared HLA-DRB1*1104-DQA1*0501-DQB1*0301 haplotype and had positive ATA, which corresponds to the strong association between ATA in white subjects and HLA-DRB1*1104, DQA1*0501, DQB1*0301 haplotype (OR = 6.93). Our patients not only shared a risky HLA haplotype for SSc but also manifested with a similar immunological activity, given that they were both positive for ATA. Although infrequent, ATA-positive SSc patients could develop scleroderma renal crisis, as in the case of the mother. Therefore, careful monitoring of the renal function is the best strategy for the case of the daughter. A positive family history is an important hint for patients suspected of autoimmune disease. The cases of familial SSc are quite rare, but they give us the opportunity to compare the genetic background, environmental risk factors, SSc phenotype, ANA type, and prevention of the complications in the course of the disease.

Characteristics of patients with systemic sclerosis living in Qatar.

Objective: The aim of this study was to determine the demographic, clinical, and immunological characteristics of patients with systemic sclerosis living in Qatar. Method: This retrospective study included 42 patients with systemic sclerosis who attended Rheumatology Clinics at Hamad General Hospital in Doha, Qatar, between January 2000 and December 2014. All patients fulfilled the 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis. Results: The 42 consecutively recruited patients of mixed ethnicities consisted of 37 (88.1%) females and 5 (11.9%) males. Of the total 42 patients, 22 (52.4%) had diffuse cutaneous systemic sclerosis (dcSSc) and 20 (47.6%) had limited cutaneous systemic sclerosis (lcSSc). Mean age at onset of first symptoms was 34.5 ± 12 years, and mean age at diagnosis was 36.1 ± 11.5 years. During follow-up, Raynaud's phenomenon occurred in 36 (85.7%) patients, sclerodactyly in 39 (92.9%) patients, digital ulcers in 16 (38.1%) patients, calcinosis in 6 (14.3%) patients, telangiectasia in 16 (38.1%) patients, and arthritis in 13 (31%) patients. The gastrointestinal and respiratory systems were the most frequently affected internal organs. Gastrointestinal involvement was present in 36 (85.7%) patients, and respiratory involvement was found in 30 (71.4%) patients. The majority of patients had positive antinuclear antibodies (ANA; 97.6%). Anti-Scl-70 antibody was found in 66.7% and anti-centromere antibody (ACA) was detected in 14.3% of the patients. Conclusion: To our knowledge, this is the first study that describes the clinical and immunological profile of patients with systemic sclerosis living in Qatar. This study cohort showed an earlier age of disease onset and diagnosis than that reported in other international studies. Furthermore, in contrast to several other studies, the diffuse type of scleroderma was more commonly observed than the limited type, which resulted in a high frequency of anti-Scl-70 antibody and interstitial lung disease.

Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease.

OBJECTIVES: We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). METHODS: Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected. RESULTS: KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10-4) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10- 4). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity. CONCLUSIONS: Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.

Oral manifestations of Systemic Sclerosis and Correlation with anti-Topoisomerase I Antibodies (SCL-70).

INTRODUCTION: Progressive systemic sclerosis (PSS) is a chronic autoimmune illness. Clinical oral manifestations in Scleroderma are very frequent. AIM: To explore the oral manifestations, frequent and rare, to investigate whether there are differences between gender and the observed correlation of changes in relation to Antibodies Anti-Topoisomerase I. MATERIAL AND METHODS: in the study were included 75 patients (65 females and 10 males), their mean age was 45.2±10, duration of illness was around 5.1±12 years diagnosed according to the ACR criteria and treated in the period 2010-2013. RESULTS: 98.7% of our patients were ANA positive, whereas 49.3% of them were Anti SCL-70 positive. Patients in 91% of cases had one or more oral manifestations of disease. The most frequent oral manifestations are: small mouth (n = 39), the lingua short frenulum (n = 21), Xerostomia (n = 24) and paradontopathia (n = 16), while more rare are: Telangiectasia (n = 14), decreased interincisal distance (n = 9), missing teeth (n = 9), absorption of dental alveoli (n = 5) and Neuralgia n. trigeminus (n = 3). Oral symptoms have been frequent in patients with Scleroderma, SCL -70 positive but not statistically significant difference. CONCLUSIONS: Oral changes have high frequency in patients with Scleroderma and these changes provide high discomfort of the mouth and lower quality of life. Oral health care to patients with Scleroderma is very important and it affects a lot in reducing the level of disease and increase the quality of life.

[High anti-topoisomerase-1 autoantibodies levels are associated with the extension of skin fibrosis and vascular progression in patients with systemic sclerosis]. / Des taux élevés d'auto-anticorps anti-topo-isomérase-1 sont associés à l'extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique.

BACKGROUND: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. METHODS: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. RESULTS: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). CONCLUSION: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

Erasmus Syndrome: A Case Series of Rare Co-Occurrence of Silicosis and Systemic Sclerosis.

Erasmus syndrome is the association of silica exposure and subsequent development of systemic sclerosis. Here we discuss five cases that presented with progressive shortness of breath, arthralgia, skin tightening, and Raynaud's phenomenon. History of exposure to silica dust was present in all cases, and further serological (Anti-Scl-70 antibody positive), radiological, and histopathological (skin biopsy) investigations confirmed the diagnosis of systemic sclerosis. Hence the diagnosis of Erasmus syndrome was made. Therefore, careful screening should be done in patients of silicosis with systemic symptoms to rule out any associated connective tissue disorder. Timely diagnosis and early intervention can prevent the patients from developing life-threatening complications and improved quality of life.

False positive anti-Topoisomerase I (Scl-70) antibody results in clinical practice: A case series from a scleroderma referral center.

PURPOSE: To determine if some patients who tested positive for anti-Scl-70 antibody in clinical practice, but did not have classifiable systemic sclerosis, were negative for anti-Scl-70 antibody by the more specific immunodiffusion method of testing. METHODS: Patients evaluated by a rheumatologist at a Scleroderma referral center who had tested positive for anti-Scl-70 antibody prior to referral, but did not have classifiable SSc based on clinical criteria, were invited to undergo testing for anti-Scl-70 antibody by immunodiffusion. Patient demographics and clinical features were recorded at the time of their evaluation, and diagnostic testing results were reviewed using the medical records. RESULTS: 52 patients were enrolled over an 8-year period, with 48 (92.3%) testing negative and 4 (7.7%) testing positive for anti-Scl-70 antibody by immunodiffusion. Of the 48 patients who tested negative, 18 (37.5%) tested negative for ANA by indirect immunofluorescence, 33 (68.8%) did not have Raynaud's phenomenon, and 43 (89.6%) had ≤1 clinical criteria items based on the 2013 ACR/EULAR SSc classification criteria. Nevertheless, 21 (43.8%) patients who were negative for anti-Scl-70 antibody by immunodiffusion had undergone a chest CT and 14 (29.2%) had undergone an echocardiogram. A total of 23 patients had at least one follow up clinic visit. 3 out of 4 patients who were positive for anti-Scl-70 antibody by immunodiffusion, but none of the 19 patients who tested negative by immunodiffusion, developed sufficient criteria during follow up to be classified as SSc. CONCLUSION: Assays for anti-Scl-70 antibody in commercial laboratories that are commonly utilized in clinical practice can produce false positive results. These results can lead to angst for patients, as well as unnecessary referrals and diagnostic evaluations.

Severe Raynaud's phenomenon from ethosuximide raised concern over possible onset of systemic vasculitis: a case report.

BACKGROUND: Ethosuximide and other anti-epileptic drugs have been reported to cause idiosyncratic reactions such as lupus-like syndromes, with elevated antinuclear antibody (ANA) levels. Herein, we present a case of a girl who developed a very severe Raynaud's phenomenon reaction and anti-Scl-70 antibodies related to treatment with ethosuximide, due to juvenile absence epilepsy (JAE). CASE PRESENTATION: A 12-year-old girl was diagnosed with JAE and treatment with ethosuximide was initiated. Two and a half months later her fingers, digits II-V bilaterally, began to ache and were discolored, alternatingly white, blue, or normal-colored. Two weeks later, her fingers were bluish-black, aching severely, almost continuously. The family sought medical advice. Ethosuximide was halted and due to the severe symptoms, treatment with both prednisolone and intravenous iloprost was commenced. Laboratory tests revealed high ANA levels with anti-Scl-70 pattern and confirmed anti-Scl-70 antibodies. After a few weeks, she started to improve and the symptoms slowly decreased over five months. Anti-Scl-70 was still detectable four months after onset of symptoms, though she was much improved. After eleven months, repeated ANA analyses were completely negative. CONCLUSION: Although extremely rare, it is important to recognize that severe Raynaud's phenomenon, threatening peripheral digital circulation, may occur as an idiosyncratic reaction to ethosuximide, raising concern over possible onset of vasculitis.

Interstitial Lung Disease in Systemic Sclerosis: A Single-center Retrospective Analysis.

BACKGROUND: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by microangiopathy, inflammation, fibrosis. Interstitial lung disease (ILD) is common among SSc patients. OBJECTIVE: This study aims to define the clinical, laboratory, and serologic characteristics of SSc patients with ILD and to present the frequency of chest computed tomography features. METHODS: Two hundred twenty-six SSc patients who applied to the Rheumatology Department between January 2007 and August 2019 were retrospectively examined. A total of 100 SSc patients with ILD (44.2%) were determined. Clinical, laboratory, and serological features of SSc patients with and without ILD were compared. RESULT: Both groups had similar characteristics in terms of age and sex. The duration of disease (p=0.001) and follow-up time (p=0.001) were longer in SSc patients with ILD. Multivariable logistic regression analysis indicated that the duration of disease (OR: 1.06 (1.01-1.13), p=0.029), presence of gastrointestinal system involvement (OR: 3.29 (1.28-8.46), p=0.013) and anti-SCL70-positivity (OR: 6.04 (2.35-15.49), p <0.001) were associated with ILD. There was an inverse relationship between Anti-CENP-B positivity and the presence of ILD (p=0.001). The assessment regarding the chest computed tomography characteristics of interstitial pneumonia patterns were as follows: 82.5% non-specific interstitial pneumonia, 14.4% usual interstitial pneumonia, and 2.1% desquamative interstitial pneumonia. The most frequent abnormal findings included ground-glass opacification (88.7%), reticulation (64.9%), traction bronchiectasis (57.7%), septal thickening (52.6%) and honeycombing (28.9%). CONCLUSION: We have shown a relationship between anti-SCL70, disease duration, gastrointestinal system involvement, and ILD in SSc patients.

Predictive value of immunological markers in systemic sclerosis.

Systemic sclerosis (SSc) is a collagenosis characterized by excessive deposition of collagen in the skin and viscera, in a background of immune disorder. The immunological profile of SSc often shows elevated levels of antinuclear antibodies (ANAs). However, many authors have identified cases of SSc having normal ANA levels, framed as paraneoplastic SSc. Among patients with negative ANAs in our group, we did not identify any neoplastic process that could support this hypothesis. The extended detection of autoantibodies is extremely useful in establishing the subset of SSc. Thus, anti-Scl70 antibodies are specific for the diffuse subset of SSc, while anticentromere antibodies (ACAs) have specificity for a limited subset. However, studies have shown the existence of cases of diffuse SSc having high titers of ACAs and cases of limited SSc with high titers of anti-Scl70 antibodies. This indicates an inconsistent association between the disease subset and the autoantibodies specific to each subset. Our study found a more balanced consistency between disease subsets and autoantibodies specific for each subset. Therefore, the percentages of patients having an immunological profile inconsistent with the subset of SSc, are lower than those found by other authors. This observation opens the perspective of larger studies on the immunological profile in SSc.

Functionally Active Antibodies to the Angiotensin II Type 1-Receptor Measured by a Luminometric Bioassay Do Not Correlate With Clinical Manifestations in Systemic Sclerosis: A Comparison With Antibodies to Vascular Receptors and Topoisomerase I Detected by ELISA.

Objectives: 1) To detect functionally active antibodies(abs) to the angiotensin II type-1-receptor (AT1R) by a novel luminometric assay. 2) To assess their prevalence in systemic sclerosis (SSc), other collagen disorders, as well as in further chronic inflammatory disorders including autoimmune, toxic and chronic viral diseases. 3) To compare these abs with anti-AT1R antibodies by ELISA as well as with antibodies to endothelin-type-A receptors (ETA1) and to topoisomerase I (topo-I) with respect to their specificity and clinical relevance. Methods: Sera from 98 SSc-patients, 110 patients with other chronic inflammatory rheumatic disorders, 97 patients with autoimmune liver diseases, 57 patients with toxic or chronic viral liver diseases and 36 healthy controls were analyzed. A luminometric bioassay was established with Huh-7-cells constitutively expressing the AT1R. Patients' sera were also tested by commercially available ELISA for anti-AT1R, -ETA1- and by an in-house ELISA for anti-topo-I-abs. Results: Fifty-two percent of the SSc-patients had functionally active anti-AT1R-abs with stimulatory (34%) or inhibitory capacity (18%). They were present also in up to 59% of patients with other rheumatic diseases but only 22% of healthy individuals (sensitivity 52%, specificity 53%). The functionally active antibodies detected by the luminometric assay did not correlate with anti-AT1R-, -ETA1- or -topo-I-abs measured by ELISA, but there was a strong correlation between anti-topo-I-, AT1R-, and -ETA1-ab reactivity measured by ELISA. Sensitivities of 55%, 28% and 47% and specificities of 66%, 87%, and 99% were calculated for these anti-AT1R-, -ETA1-, and anti-topo-I-abs, respectively. Functionally active abs did not correlate with disease severity or any organ manifestation. In contrast, abs to topo-I, AT1R, and ETA1 were associated with digital ulcers, pulmonary- and esophageal manifestation. Conclusions: Functionally active anti-AT1R-abs can be detected in SSc-patients but do not correlate with disease activity. They are not specific for this disease and occur also in other autoimmune disorders and even viral or toxic diseases. Also, the vascular antibodies detected by ELISA are not SSc-specific but correlated with disease manifestations. In contrast, anti-topo-I-abs were confirmed to be a highly specific biomarker for both, diagnosis and organ manifestations of SSc.

Increased malignancies in our Waikato cohort of patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) has been associated with an increased risk of malignancy (especially in the skin, lung, breast, and hematological system). AIM: To determine the risk of malignancies in our SSc cohort. METHODS: The NZ National Cancer Registry supplied details of all malignancies recorded in patients attending the Waikato Hospital Systemic Sclerosis Clinics from 2005 to 2018. Prospectively gathered clinical data were used to look for associations between clinical variables and malignancy. RESULTS: Out of the 164 patients in the Waikato SSc cohort, 32 (19.5%) had developed a malignancy. The overall standardized incidence rate was found to be 2.2 (95% CI 1.4-3.4) but was higher for men (4.4, 95% CI 1.4-10.3). The absolute numbers of patients with SSc and malignancies were small and were not adequately powered to investigate the SSc subgroups. The mean age of patients with malignancy was approximately 8 years older than patients without. The most common form of malignancy was skin (14, 43.7%), followed by breast (6, 18.7%), and lymphoma (5, 15.6%). CONCLUSION: This study found an increased risk of malignancy for patients within the Waikato SSc cohort. Risk was greater in male patients and the mean age of patients with malignancies was approximately 8 years older than those without malignancy.

Antinuclear Antibody Tests.

The presence of antinuclear antibodies (ANAs), which include autoantibodies to extractable nuclear antigens (ENAs), in the sera of patients with connective tissue diseases provides useful immunologic and pathophysiologic insight into the nature of their disease. This article discusses the most commonly used diagnostic modalities for detecting and quantitating the presence of ANA: indirect immunofluorescence assay, enzyme-linked immunosorbent assay, and multiplex bead technology, which serve as useful screening tests. We also review testing for autoantibodies to ENAs, which are often helpful to confirm the diagnosis of a specific connective tissue disease.

Complex assessment of bone mineral density, fracture risk, vitamin D status, and bone metabolism in Hungarian systemic sclerosis patients.

OBJECTIVE: We wished to determine bone alterations in systemic sclerosis (SSc) patients by conventional densitometry (DXA), peripheral quantitative computed tomography (pQCT), and bone biomarkers. METHODS: We included 44 SSc patients and 33 age-matched healthy controls. Lumbar spine and femoral neck bone mineral density (BMD) was assessed by DXA. Volumetric BMD was measured by pQCT at the radius. FRAX, 25-hydroxyvitamin-D3 (25-OH-D3), parathyroid hormone, osteocalcin, C-terminal collagen telopeptide, and procollagen type I amino-terminal propeptide were also assessed. RESULTS: SSc patients had lower L2-4 BMD (0.880 ± 0.108 vs. 0.996 ± 0.181 g/cm2; p = 0.019) and femoral neck (FN) BMD (0.786 ± 0.134 vs. 0.910 ± 0.090 g/cm2; p = 0.007) by DXA. In SSc vs. controls, pQCT indicated lower mean cortical (328.03 ± 103.32 vs. 487.06 ± 42.45 mg/cm3; p < 0.001) and trabecular density (150.93 ± 61.91 vs. 184.76 ± 33.03 mg/cm3; p = 0.037). Vitamin D3 deficiency was more common in SSc vs. controls (60.0% vs. 39.3%; p = 0.003). L2-4 (p = 0.002) and FN BMD (p = 0.015) positively correlated with BMI. pQCT assessments confirmed an inverse correlation between pulmonary manifestation and total (p = 0.024), trabecular (p = 0.035), and cortical density (p = 0.015). Anti-Scl70 positivity inversely correlated with pQCT total density (p = 0.015) and the presence of digital ulcers with cortical density (p = 0.001). We also found that vertebral and FN BMD as determined by DXA significantly correlated with pQCT total, trabecular, and cortical density (p < 0.05). CONCLUSION: The results of our study suggest that bone loss in SSc patients may be associated with lower BMI, anti-Scl70 positivity, and the presence of pulmonary manifestations and digital ulcers. Both DXA and pQCT are appropriate tools to evaluate the bone alterations in SSc patients.

Unique clinical and autoantibody profile of a large Asian Indian cohort of scleroderma-do South Asians have a more aggressive disease?

AIM AND METHODS: A single-centre retrospective study was conducted using electronic medical records (EMR) of inpatients and outpatients with the diagnosis of "scleroderma" or "systemic sclerosis" visiting our clinic over the preceding 5 years. RESULTS: A total of 327 patients' charts met our selection criteria; 301 were females. The median (IQR (inter quartile range)) age at onset of first non-Raynaud's symptom was 34.67 (27-43) years and median (IQR) disease duration prior to presentation to our department was 2.5 (1-5) years. Of these, 310 (94.8%) belonged to diffuse systemic sclerosis variety, 13 (4%) had limited systemic sclerosis, and 4 (1.2%) were of sine scleroderma type. A total of 289/302 (95.7%) patients were positive for ANA; of them, 245/327 (74.9%) were Scl-70 antibody-positive and 4% were CENP antibody-positive. Interstitial lung disease (ILD) was present in 288/327 (88.1%) patients. Among patients with available baseline forced vital capacity (FVC) data, 20% had a normal lung function and 28.4% had severe restriction. Pulmonary hypertension as assessed by echocardiography was present in 8.1% of patients. A significant association of Scl-70 antibody positivity with the presence of interstitial lung disease (ILD) (p = 0.000) and pulmonary hypertension (p = 0.035) was seen. On the other hand, presence of CENP antibody showed a protective trend against muscle weakness and/or muscle enzyme elevation (p = 0.052). Presence of arthritis was protective against development of digital ulceration (p = 0.021) and PAH (0.004). Patients younger than 40 years of age had significantly higher frequency of Scl-70 positivity (p = 0.038), whereas CENP antibody positivity was more likely in those aged > 40 years (p = 0.002). CONCLUSION: Younger age of onset and high prevalence of Scl-70 antibody are unique South Asian features common with large Indian, Thai, and Chinese series. High prevalence of ILD is a feature common to Indian and Chinese series. Strong correlation of Scl-70 antibody with younger age and pulmonary hypertension were unique features of our cohort. KEY POINTS: • Asian Indian scleroderma patients are younger by 2 decades compared to Caucasian series. • Higher prevalence of Scl-70 antibody, its association with young age, interstitial lung disease and pulmonary hypertension are features of our cohort. • High prevalence of interstitial lung disease (88.1%) was noted ; among those with baseline spirometry data (141/327), two thirds(66%) had moderate to severe restriction. • Younger age at onset, higher prevalence of Scl-70 antibody are features common to other Indian, Thai and Chinese series.

[Cancers in systemic sclerosis : risk factors, impact on survival and literature review]. / Survenue de cancers au cours de la sclérodermie systémique : facteurs de risque, impact sur la survie et revue de la littérature.

INTRODUCTION: Patients with systemic sclerosis (SSc) have an increased risk of malignancy. In this study, we aimed to analyze the prevalence of cancer, the risk factors and the impact on overall survival. PATIENTS AND METHODS: We analyzed clinical (history of cancer, toxic exposition, organ involvement), immunological and treatment data in a monocentric cohort of SSc patients followed between January 2004 and December 2017. RESULTS: Two hundred and ten patients with SSc were included. During the follow-up, twenty-one patients (10 %) were diagnosed with malignancies. The underlying malignancies were breast adenocarcinoma (n=6, 28%), lung cancer (n=6, 28%), colorectal (colic adenocarcinoma, carcinoid tumor of the appendix), ovarian and cervix uteri, melanoma, kidney and papillary thyroid carcinoma (one of each). The median time between the first visit and the diagnosis of cancer was 4 [2-10] years. The overall survival in SSc patients with cancer was not significantly different from patients without cancer, with median survival during the first quartile (75%) at 12 years for patients with cancer and 11.6 years for those without cancer (P=0.9). The history of renal scleroderma crisis (HR 10.99, IC95% [1.95-62.07]; P=0.006) and the presence of anti-topoisomerase I antibodies (HR 5.5, IC95% [1.40-21.67]; P=0.01) were associated with an increased risk of cancer, whereas the presence of gastroesophageal reflux was inversely associated with the cancer occurrence (HR 0.22, IC95% [0.056-0.867]; P=0.03). CONCLUSION: The history of renal scleroderma crisis and the positivity of anti-topoisomerase I antibodies were associated with an increased risk of cancer in SSc patients in this monocentric study.

Prevalence of antibodies to ganglioside and Hep 2 in Gaucher, Niemann - Pick type C and Sanfilippo diseases.

Lysosomal Storage Diseases (LSDs) are rare genetic diseases, the majority of which are caused by specific lysosomal enzyme deficiencies and all are characterized by malfunctioning lysosomes. Lysosomes are key regulators of many different cellular processes and are vital for the function of the immune system. Several studies have shown the coexistence of LSDs and immune abnormalities. In this study, we investigated the presence of autoantibodies in the plasma of patients with Gaucher disease (GD; n = 6), Sanfilippo Syndrome B (SFB; n = 8) and Niemann - Pick type C disease (NPC; n = 5) before and following Miglustat treatment (n = 3). All were examined for antibodies to antigens of Hep-2 cells and antiganglioside antibodies (AGSA). No autoantibodies were detected in GD patients. 3/8 SFB patients showed only AGSA (2/3 IgM / IgG; 1/3 IgG), 3/8 only anti-Sm E/F and 2/8 showed both IgM / IgG or IgG AGSA and anti-Sm E/F. 3/5 NPC patients showed AGSA (2/3 IgM and IgG, 1/3 IgM) and one anti-Sm E/F and IgM AGSA. Following treatment one patient with no AGSA developed IgM AGSA and two with both IgG and IgM showed only IgG AGSA. In our study, investigating similar numbers of patients, autoantibodies were observed in NPC and SFB patients but not in GD patients. Our findings suggest that, independently of the development of an autoimmune disease in patients with LSDs, there seems to be an autoimmune activation that differs in different disorders. Further studies including more patients, also at different stages of disease and treatment, are needed in order to get further insight into the immune irregularities associated with different LSDs and their significance.

Clinical evaluation of CENP-B and Scl-70 autoantibodies in silicosis patients.

Silicosis patients (SIL) suffer from respiratory disorders and dysregulation of autoimmunity. Frequent complications such as rheumatoid arthritis, systemic sclerosis (SSc) and vasculitis are known in SIL. Furthermore, we reported previously that some SIL exhibited better respiratory conditions in association with a worse immunological status. In this study, the clinical roles of anti-CENP-B and Scl-70 autoantibodies in SIL were analyzed. The titer index (Log10) of anti-CENP-B autoantibody in SIL was higher than that of healthy volunteers (HV), and that of SSc was higher than those of HV and SIL. This titer index was positively correlated with an assumed immune status of 1 for HV, 2 for SIL, and 3 for SSc. Moreover, although factor analysis revealed that the titer index of the anti-CENP-B autoantibody formed the same factor with the anti-Scl-70 autoantibody, IgG value and age in SIL cases, another extracted factor indicated that the IgA value and anti-Scl-70 antibody were positively related, but anti-CENP-B showed an opposite pattern in the results of the factor analysis. These findings indicated that the titer index of anti-CENP-B autoantibody may be a biomarker for dysregulation in SIL cases. Future clinical follow-up of SIL may therefore require both respiratory and immunological assessment.