Search

Vaccination has been a game changer in our efforts to address the coronavirus disease 2019 (COVID-19) pandemic. However, the disease might still represent a clinical crisis for several more years, in part because of the inevitable emergence of variants capable of evading the preexisting immunity. Drugs affecting viral spread will help curtail transmission, but therapeutics are needed to treat the more severe cases requiring hospitalization. A deep analysis of the evolving immune landscape of COVID-19 suggests that understanding the molecular bases of the distinct clinical stages is paramount if we are to limit the burden of inflammation, which can lead to death in frail individuals, according to age, sex, and comorbidities. Different phases can be defined using immune biomarkers and need specific therapeutic approaches, tailored to the underlying immune contexture.

Objective: To evaluate the clinical effectiveness of golimumab in biologic inadequate responder (IR) patients with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA). Methods: We analyzed 1424 patients on golimumab from the GISEA registry. Drug survival was estimated by Kaplan-Meier analysis in biologic-naïve, 1-biologic IR, ≥ 2-biologics IR patients. Hazard ratios (HRs) of discontinuing golimumab at 2 years were assessed by multivariate Cox regression. Patients achieving CDAI based low disease activity (LDA) or BASDAI < 4 were calculated at 6 and 12 months. Results: In RA (n.370), the 2-years survival on golimumab was 61.4% in 1-biologic IR, 51.9% in ≥ 2-biologics IR, and 73.1% in biologic-naive patients (P = 0.002 vs ≥ 2-biologics IR). In SpA (n.502), the survival was similar among 1-biologic IR (80%), ≥ 2-biologics IR (76.5%), and biologic-naive (74.6%) patients (P > 0.05). In PsA (n.552) the survival was 72% in 1-biologic IR, 72.5% in ≥ 2-biologics IR, and 71.8% in naïve-biologic (P > 0.05). Predictors of golimumab discontinuation were monotherapy (HR 1.65) for RA, female gender for SpA (HR 2.48) and PsA (HR 1.57). In RA, patients on CDAI-LDA were lower in 1-biologic IR (40%) or ≥ 2 biologics IR (40%) than in biologic-naïve (60%) group at 6 months (P = 0.02), but no difference was observed at 12 months. In PsA and SpA, the percentage of patients on CDAI-LDA or BASDAI < 4 at 6 months was almost identical across the subgroups. Conclusions: Golimumab had similar effectiveness in biologic-failure and biologic-naïve SpA and PsA, but seems to be less effective in multi-failure RA patients, especially as monotherapy. The best outcomes were seen in male patients.

NA

Not applicable

COVID-19 pandemia is a major concern for patients and healthcare systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analysing the basic biology of single diseases, the data suggest that there is an "immunological umbrella" that seems to protect against the infection, through IFN type 1 and NK cell function. To date, reports from China, United States and Europe did not reveal an higher risk of infection, either for rheumatoid arthritis, juvenile idiopathic arthritis nor for lupus erythematosus. Antimalarials, anti-IL6-Anti-IL6 receptor, anti-IL1, anti-GM-CSF receptor and JAK1/2/3 inhibitors, are under investigation in COVID-dedicated clinical trials to control the inflammation raised by SARS-CoV-2 infection. Initial reports on the occurrence of autoimmune phenomena in the convalescence phase of SARS-CoV-2 infection suggests that the immunological consequences of the infection need to be strictly understood. Reporting of the study conforms to broad EQUATOR guidelines (Simera et al January 2010 issue of EJCI).

N/A

Objective. Systemic sclerosis (SSc) is a rare multi-organ disorder with a prominent gastrointestinal (GI) involvement. Altered gut microbiota is now considered a pivotal factor associated with the development of immune-mediated and inflammatory diseases. We performed a 16S ribosomal RNA (rRNA) gene-sequencing analysis of fecal microbiota in a cohort of SSc patients and matched healthy controls (HCs), with the aim to obtain some hints about a possible role of dysbiosis in the onset, progression, and severity of the disease. Methods. We analysed stool samples from 63 SSc patients with different disease duration, phenotype, and nutritional status and from 17 HCs through 16S ribosomal RNA (rRNA) gene-sequencing. Results. Microbial richness was lower for patients with long-standing disease. A similar observation was made for patients with diffuse cutaneous SSc (dsSSc) compared to those with limited variant (lcSSc) and for patients who reported a recent weight loss. Consistent with previous reports, we noted a deviation of the intestinal microbial composition in patients with SSc compared to HCs, with a greater expression of Lactobacillus and Streptococcus and a depletion of Sutterella. Nutritional status, assessed using BMI as a surrogate, appeared to have a marked impact on the gut microbiota, with overweight patients showing lower richness compared both to underweight and normal-BMI patients. Conclusion. Our findings expand the current knowledge of gut microbiota in SSc and could be useful to identify patients who would most benefit from treatments aimed at restoring the eubiosis.

Immune related adverse events (irAEs) have been observed with all checkpoint inhibitors and are very frequent. The evidences coming from experimental models of congenital or acquired deficiency of CTLA-4 or from PD-1 knock-out mice, provided all the informations to interpret the organ or systemic manifestations (endocrine, or systemic autoimmune chronic inflammatory diseases-ACIDs) observed in trials as well as in registries of cohorts treated with anti-CTLA-4 or anti-PD-1/PD-L1 inhibitors, or combination therapies. Finally the concern raised by cancers occurring in patients with autoimmune diseases (Systemic Lupus Erythematosus, Myositis, Rheumatoid Arthritis, Psoriatic Arthritis, Vasculitis, Scleroderma, Polymyalgia Rheumatica and others) and how to deal with immunotherapy was discussed. The biological knowledges acquired with the immunotherapy trials, have paved to way to better treat autoimmune diseases in patients developing cancer during the autoimmune illness. Immunotherapy without Autoimmunity is the unmet need within our reach in the future.

This post hoc analysis of the phase III Active PSoriaTic Arthritis RAndomizEd TriAl (ASTRAEA) evaluated the effect of baseline body mass index (BMI) on subsequent response to subcutaneous (SC) abatacept in patients with psoriatic arthritis (PsA). Methods In ASTRAEA, patients with active PsA were randomised (1:1) to receive blinded weekly SC abatacept 125 mg or placebo for 24 weeks. Treatment response at week 24 was assessed by the proportions of patients achieving American College of Rheumatology 20% improvement response, Disease Activity Score in 28 joints (DAS28 (C reactive protein (CRP))) ≤3.6 and <2.6, Health Assessment Questionnaire-Disability Index reduction from baseline ≥0.35 and radiographic non-progression (defined as change from baseline ≤0 in PsA-modified total Sharp/van der Heijde score). Responses were stratified by baseline BMI (underweight/normal, <25 kg/m 2; overweight, 25-30 kg/m 2; obese, >30 kg/m 2) and compared in univariate and multivariate models. Results Of 212/213 and 210/211 patients with baseline BMI data in the abatacept and placebo groups, respectively, 15% and 19% were underweight/normal, 36% and 27% were overweight, and 49% and 54% were obese. After adjusting for baseline characteristics, there were no significant differences for any outcome measure at week 24 with abatacept in the overweight or obese versus underweight/normal subgroup. In the placebo group, patients in the obese versus underweight/normal subgroup were significantly less likely to achieve DAS28 (CRP) <2.6 at week 24 (OR 0.26; 95% CI 0.08 to 0.87; p=0.03). Conclusion BMI does not impact clinical or radiographic response to SC abatacept in patients with PsA. Trial registration number NCT01860976.

Background: Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Ab neg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Ab neg RA and test their predictive value of therapeutic response. Methods: Thirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Ab neg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68 + , CD3 + , CD20 + , CD21 + , CD117 + , and CD138 + cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Ab neg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations. Results: At study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68 + and sublining CD21 + , CD20 + , and CD3 + cells than Ab neg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117 + cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Ab neg RA patients. Conversely, Ab neg RA patients showed higher IHC score of CD138 + cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3 + cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Ab neg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of subl

We have evaluated long-term retention rate of anakinra in adult onset Still disease and predictive factors for treatment response. The risk of losing anakinra efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of anakinra withdrawal.

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD); however, withdrawal owing to long-term remission as well as lack or loss of efficacy and adverse events may variably impact treatment survival. Objectives: Aims of this study were: i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); ii) to identify predictive factors of lack of efficacy, loss of efficacy and ANA withdrawal owing to long-term remission. Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed. Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96±36.05 months were enrolled. The overall DRR of ANA was 44.6% and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: i) biologic naïve patients and those previously treated with other biologics (log-rank p=0.97); ii) monotherapy and concomitant use of cDMARDs (log-rank p=0.45); iii) systemic and chronic articular types of AOSD (log-rank p=0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p=0.01, OR=1.194, C.I. 1.043-1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p=0.03, OR=0.224, C.I. 0.058-0.863). Conclusions: Long-term DRR of ANA has been f

Objectives: To define baseline clinical and immunological characteristics [anti-citrullinated peptide antibodies (ACPAs), immunoglobulin M (IgM)- and IgA-rheumatoid factor (RF), and interleukin-6 (IL-6) levels] involved in determining baseline erosiveness, outcome, and radiographic progression among seropositive and seronegative early rheumatoid arthritis (ERA) patients.Method: The 408 ERA patients enrolled in the study were monitored every 3months according to the treat-to-target strategy. At baseline and after 12months, hand and foot radiographs were evaluated using the Sharp/van der Heijde erosion score.Results: At diagnosis, seronegative patients were older and had higher Disease Activity Scores (DASs) than seropositive patients. A higher risk of erosiveness at baseline was conferred by IgA-RF positivity and IL-6 plasma levels 7.6pg/mL, particularly when simultaneously present. In multivariate analysis, disease duration and IL-6 plasma levels 7.6pg/mL arose as independent variables associated with presence of erosions at onset. Radiographic progression at 1year follow-up, which occurred in 11.1% of ERA patients, was predicted by ACPA positivity, together with higher age at diagnosis. Despite similar percentages of good European League Against Rheumatism response, DAS and Boolean remission being observed over time among seropositive and seronegative patients and between erosive and non-erosive subjects, ERA patients who were erosive at onset, IgA-RF seropositive, and simultaneously having high baseline IL-6 plasma levels (7.6pg/mL) were treated to a greater extent with tumour necrosis factor blockers after 12months.Conclusion: IgA-RF positivity and IL-6 plasma levels are crucial for baseline erosiveness, while ACPA positivity represents the strongest risk factor for developing radiographic progression in ERA.

Background: The purpose of this study was to investigate the frequency and the distribution of inflammatory cell infiltrate in two sets of cutaneous biopsies derived from clinically involved and uninvolved skin of patients with systemic sclerosis (SSc) and to find correlations between the cell infiltrate and the progression of skin involvement. Methods: Immunohistochemistry was carried out to identify CD68, CD3, CD20 and CD138-positive (+) cells in clinically involved and uninvolved skin of 28 SSc patients. Patients were followed for 6 months and the characteristics of the infiltrate were analyzed according to disease duration, clinical features and skin involvement progression. Results: In all SSc cutaneous specimens, cellular infiltrates were found in a perivascular location predominantly in the mid and deeper portions of the dermis. All the analysed biopsies showed a CD3+ and CD68+ cell infiltrate and the mean number of CD3+, as well as CD68+ cells, was higher in clinically involved skin (CD3+: 71.7±34.6 and CD68+: 26.3±8.4) than in clinically uninvolved skin (CD3+: 45.7±36.0; CD68+: 13.6±6.1), (p<0.001 for both comparisons). CD20+ cells were found in 17 (60.7%) patients and in these patients the mean number of CD20+ cells was higher in involved (4.7±5.9) than in uninvolved skin (1.9±2.9), (p=0.04). Early SSc had a greater number of CD20+ cells compared with patients with long-standing disease. CD138+ cells were found in 100% of involved skin biopsies and in 89.3% of uninvolved skin samples. The mean number of CD138+ cells was higher in clinically involved skin (3.6±2.3) than in clinically uninvolved skin (1.9±1.7), (p<0.001). Considering the 7 patients that experienced a worsening of skin score higher than 20% after 6-month of follow-up, all of them had presented a CD20+ skin infiltrate in the involved skin biopsy. Conclusions: Our results confirm that mononuclear cells are present in the skin of all SSc patients underlining the role of inflammatory cell i

Objective: Paradoxical arthritis under TNF-inhibitor (TNF-i) for Inflammatory Bowel Disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial (ST) and colonic mucosa (CM) tissues in IBD patients developing paradoxical arthritis under TNF-i. Methods: IBD patients without history of co-existing joint involvement who developed arthritis under TNF-i, were enrolled. Each patient underwent ST biopsy and ileo-colonoscopy with CM biopsies. ST and CM paired samples were stained through immunohistochemistry(IHC) for CD68, CD21, CD20, CD3 and CD117. Clinical and immunological parameters [Anti-citrullinated peptides antibodies(ACPA)-IgM/IgA Rheumatoid Factor(RF)] were collected. Psoriatic Arthritis(PsA) and ACPA/IgM-RF/IgA-RF negative Rheumatoid Arthritis(RA) were enrolled as comparison. Results: 10 patients with IBD [46.0 +- 9.7 years old, 13.2 +- 9.9 years of disease duration, 2.5 +- 1.6 years of TNF-i exposure, 6 with Crohn’s Disease and 4 with Ulcerative Colitis respectively] were studied. At ST level, IHC revealed that IBD patients with paradoxical arthritis showed more similar histological findings in terms of synovial CD68+, CD21+, CD20+, CD3+ and CD117+ cells compared to PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing the CM specimens, IBD patients showed presence of CD68+, CD3+, CD117+ and CD20+ cells in 100%, 70%, 60% and 50% of cases, respectively, despite endoscopic remission. Finally, addition of c-DMARDs and switch to Ustekinumab were more effective than swapping into different TNF-i in IBD patients with paradoxical arthritis. Conclusion: IBD patients may develop histologically proven synovitis during TNF-i, comparable to PsA. The inhibition of inflammatory pathways alternative to TNF (IL12/1L23) may be an effective therapeutic option for severe paradoxical articular manifestations.

OBJECTIVES: To define baseline clinical and immunological characteristics [anti-citrullinated peptide antibodies (ACPAs), immunoglobulin M (IgM)- and IgA-rheumatoid factor (RF), and interleukin-6 (IL-6) levels] involved in determining baseline erosiveness, outcome, and radiographic progression among seropositive and seronegative early rheumatoid arthritis (ERA) patients. METHOD: The 408 ERA patients enrolled in the study were monitored every 3 months according to the treat-to-target strategy. At baseline and after 12 months, hand and foot radiographs were evaluated using the Sharp/van der Heijde erosion score. RESULTS: At diagnosis, seronegative patients were older and had higher Disease Activity Scores (DASs) than seropositive patients. A higher risk of erosiveness at baseline was conferred by IgA-RF positivity and IL-6 plasma levels ≥7.6 pg/mL, particularly when simultaneously present. In multivariate analysis, disease duration and IL-6 plasma levels ≥7.6 pg/mL arose as independent variables associated with presence of erosions at onset. Radiographic progression at 1 year follow-up, which occurred in 11.1% of ERA patients, was predicted by ACPA positivity, together with higher age at diagnosis. Despite similar percentages of good European League Against Rheumatism response, DAS and Boolean remission being observed over time among seropositive and seronegative patients and between erosive and non-erosive subjects, ERA patients who were erosive at onset, IgA-RF seropositive, and simultaneously having high baseline IL-6 plasma levels (≥7.6 pg/mL) were treated to a greater extent with tumour necrosis factor blockers after 12 months. CONCLUSION: IgA-RF positivity and IL-6 plasma levels are crucial for baseline erosiveness, while ACPA positivity represents the strongest risk factor for developing radiographic progression in ERA.

Acute inflammation is a complex and tightly regulated homeostatic process that includes leucocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as rheumatoid arthritis (RA), it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells, including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contri

Analysis of B cell activating factor (BAFF) receptors before and after B cell depletion therapy (BCDT) might offer a clue to the understanding of whether some B cell subsets may represent useful biomarkers of biological and clinical responses. Among the BAFF receptors in a cohort of rheumatoid arthritis (RA) patients, the AA have shown, by fluorescence activated cell sorter (FACS) analysis of median fluorescence intensity (MFI), that transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) do not change, whereas the most important, BAFF receptor 3 (BR3), appears to be decreased before as well as after BCDT in all B cell subsets but not in plasmablasts, the most important subset, depleted by BCDT.

Objectives: To assess the long-term efficacy and safety of single and multiple courses of rituximab therapy in systemic sclerosis (SSc) patients with and without lung disease. Methods: A total of 20 SSc patients with a diffuse disease were treated with rituximab. At baseline and during follow-up the lung involvement was evaluated with pulmonary function tests (FVC and DLCO) and with lung high-resolution computed tomography (HRCT). Results: The skin score, activity, and severity indices improved significantly after 12 months and at final follow-up compared to baseline.After 12 months, there was a significant increase of FVC and TLC compared to baseline (. p = 0.024 and p = 0.005, respectively), while the mean DLCO value remained stable.Considering the last available follow-up in six patients with restrictive lung disease at baseline, two patients (33.3%) experienced an increase of more than 10% of FVC, one patient had a decrease of FVC >10%, while in three patients FVC remained stable (50%). After the mean follow-up of 48.5 ± 20.4 months, among the patients with normal lung parameters at baseline, FVC remained stable in 12 (85.7%) and in one patient (14.3%) it increased by more than 10%. At the final follow-up, the alveolar and interstitial HRCT scores remained stable in more than 80% of patients, both in patients with and without restrictive lung disease at baseline. Conclusions: Anti-CD20 B cell depletion therapy is effective on skin involvement but seems also to preserve the pulmonary function, as supported by a stable or improved FVC and stable interstitial score, suggesting a possible role of rituximab as a modifying therapy overall in early diffuse SSc.

Objective: To investigate the relationship of the polymorphic enhancer HS1,2 central to the 39 enhancer complex regulatory region ( IgH3'EC) of the immunoglobulin heavy chain genes with systemic sclerosis (SSc) disease and compare it with HLA-DR and DQ associations.Methods: A total of 116 patients with SSc were classified as diffuse (dSSc) or limited (lSSc), and as carriers of antitopoisomerase I (anti-Scl70) or anticentromere (ACA) antibodies. Allele and genotype frequencies were assessed in the population as a whole and in the two major subsets, dSSc and lSSc. The concentration of peripheral blood immunoglobulin levels was also determined and analysed according to the genotypes.Results: The analysis of genotypes for the four alleles of the HS1,2A enhancer showed an increased frequency of allele *2 in the SSc cohort highly significant versus controls (57% vs. 40%, p < 0.0001). Considering the autoantibody pattern, we found that the frequency of the 2/2 genotype was increased in ACA+ patients (42%) and anti-Scl70+patients (31%) compared with the control group (15%). The differences of allelic frequencies among dSSc versus lSSc or ACA+ versus anti-Scl70+ patients were not significant, although highly significant when comparing each subgroup with the control group. HLA-DRB1*11 and DQB1*03 associated with SSc. No association was seen between HS1,2A enhancer polymorphism and HLA alleles.Conclusions: These data confirm there was an increased risk of having SSc in carriers of allele *2, suggesting an intriguing function of this polymorphism for B-cell regulation.

Objective: To investigate the relationship of the polymorphic enhancer HS1,2 central to the 39 enhancer complex regulatory region ( IgH3'EC) of the immunoglobulin heavy chain genes with systemic sclerosis (SSc) disease and compare it with HLA-DR and DQ associations.Methods: A total of 116 patients with SSc were classified as diffuse (dSSc) or limited (lSSc), and as carriers of antitopoisomerase I (anti-Scl70) or anticentromere (ACA) antibodies. Allele and genotype frequencies were assessed in the population as a whole and in the two major subsets, dSSc and lSSc. The concentration of peripheral blood immunoglobulin levels was also determined and analysed according to the genotypes.Results: The analysis of genotypes for the four alleles of the HS1,2A enhancer showed an increased frequency of allele *2 in the SSc cohort highly significant versus controls (57% vs. 40%, p < 0.0001). Considering the autoantibody pattern, we found that the frequency of the 2/2 genotype was increased in ACA+ patients (42%) and anti-Scl70+patients (31%) compared with the control group (15%). The differences of allelic frequencies among dSSc versus lSSc or ACA+ versus anti-Scl70+ patients were not significant, although highly significant when comparing each subgroup with the control group. HLA-DRB1*11 and DQB1*03 associated with SSc. No association was seen between HS1,2A enhancer polymorphism and HLA alleles.Conclusions: These data confirm there was an increased risk of having SSc in carriers of allele *2, suggesting an intriguing function of this polymorphism for B-cell regulation.

OBJECTIVE: Osteoarthritis and osteoporosis are two major health problems affecting postmenopausal women. Epidemiological observations seem to demonstrate a possible inverse relationship between osteoarthritis and osteoporosis. Erosive osteoarthritis (EOA) of the hand is a destructive form of primary osteoarthritis. This study evaluated bone mineral density and bone metabolism changes in erosive and nonerosive hand osteoarthritis women. DESIGN: Fifty-five women (mean age, 59 years; body mass index, 23 ± 1.4 kg/m2) who had been postmenopausal for an average of 9 years and who presented with hand osteoarthritis according to American College of Rheumatology criteria were enrolled in the study; 15 women showed clinical and radiological evidence of hand EOA. Twenty women matched for age, age at menopause, and body mass index formed the control group. Bone mineral density (g/cm2) was measured at the hip and lumbar spine using dual-energy x-ray absorptiometry. Serum and urinary calcium and phosphate, serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, and urinary breakdown products of bone matrix (CrossLaps) were analyzed. RESULTS: Women with hand EOA had a statistically significant lower T- and Z-score L2-L4 value than non-hand EOA women and controls (P < 0.01). Moreover, postmenopausal women with hand EOA had higher significant percentage of osteoporosis at lumbar spine when compared with non-hand EOA postmenopausal women and controls. Any statistically significant difference in osteocalcin and CrossLaps serum levels was noted among women with hand EOA, hand osteoarthritis, and controls. CONCLUSIONS: Our data suggest that postmenopausal women with clinical and radiological EOA are at risk for development of osteoporosis. © 2006 by The North American Menopause Society.