Association of MICA alleles with psoriatic arthritis and its clinical forms. A multicenter Italian study.

OBJECTIVE: Analysis of the association between psoriatic arthritis (PsA) clinical forms and MICA gene transmembrane polymorphisms. METHODS: Patients were classified as having peripheral asymmetric oligoarthritis (AO), peripheral symmetric poly-arthritis (PA) and spondylitis (SP), or disease combinations (PA/SP, OA/SP). Two hundred and twenty-six patients with PsA were typed for MICA exon 5 microsatellite (TM) by heteroduplex analysis and compared with 225 normal controls. RESULTS: MICA-TM microsatellite typing revealed that, among the different clinical forms of PsA, only the combined PA/SP subset shows a significant positive association with MICA-A9 and a lower frequency of MICA-A4, A5 genotype in PsA patients with a decrease, only in the PA/SP cohort, of all MICA-A5 combinations except MICA-A5, -A9. CONCLUSION: These results suggest a role for genes within the HLA region in the pathogenesis of PsA, and reinforce the idea that the different forms of PsA may have heterogeneous genetic basis.

[Role for familial and genetic features in the therapeutic response of psoriatic arthritis]. / Valutazione della familiarità e dell'assetto genetico per la risposta terapeutica dell'artrite psoriasica.

AIM OF THE STUDY: To analyze PsA patients with and without a familiar distribution for Ps and PsA, in order to better evaluate the genetic data, to verify the existence of different expression of the disease and finally to define the susceptibility to treatment in these patients. MATERIALS AND METHODS: 230 PsA patients were selected for familiar or sporadic distribution of the disease and were evaluated for the main clinical, demographic, radiological and laboratory features, as well as for the ongoing treatments. In each patient HLA class I (A,B,C) and II (DRB1, DQB1) antigens were typed with PCR-SSP method while MICA-A exon 5 microsatellite typing was performed by heteroduplex analysis in 122 subjects. RESULTS: A familiar distribution for Ps and PsA was found in 68 patients (29.6%) although only two patients had familiarity for PsA. In the familiar PsA group the male prevalence was significantly higher respect to the sporadic one (p<0.001) and the more frequently involved relative was the father (28%). Mean age (p<0.006) and age at onset of Ps (p<0.004) and PsA (p<0.014) were significantly lower in familiar respect to sporadic PsA. Between the two groups no difference was found concerning the articular involvement, the radiological findings, the disease activity (including number of painful/swollen joints), the inflammatory laboratory parameters (including ESR and CRP) and genetic aspects, including the frequencies of MICA-A alleles that were analysed in 30 patients with the familiar form and in 92 with the sporadic one. In the follow-up the therapeutic response to any evaluated treatment adopted for PsA did not show any significant difference in the two groups. All these results were confirmed even when the patients in the two groups were matchable for sex, age and disease duration. CONCLUSION: Our results confirm that familiar PsA is characterized by an early onset of the disease and by a male and fatherly predominance respect to the sporadic form, although the clinical-radiologic findings, the genetic typing and the therapeutic response do not permit us to identify any particular subset.

Natural killer cells and gamma/delta T cells in synovial fluid and in peripheral blood of patients with psoriatic arthritis.

OBJECTIVE: NK surface markers and gamma/delta TCR antigen are involved in non-MHC-restricted cytotoxicity, which represents a major effector mechanism of the cell-mediated immune response. We evaluated in PsA patients SF and PB lymphocytes expressing these cellular subsets in order to obtain information on the possible role played by them in the disease. METHODS: We studied 29 PsA and 27 RA patients, as well as 27 healthy controls. In 17 PsA and 16 RA patients with knee joint effusion, analysis of SF was performed. SF and PB lymphocyte analysis was performed by direct dual immunofluorescence flow cytomettry using anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-TCR-gamma/delta-1 and anti-CD16 and anti-CD56 monoclonal antibodies. RESULTS: PsA and RA patients had, with respect to controls, lower values (both as percentages and in absolute numbers) of PB T cells expressing gamma/delta TCR. SF Iymphocytes of PsA and RA patients were characterised, as compared to PB lymphocytes, by lower numbers (both in absolute numbers and in relative terms) of NK and NK-T cells. Considering the absolute numbers of the various lymphocyte subsets, a strong correlation was found in PsA SF between gamma/delta T cells and NK (p < 0.0007) or NK-T cells (p < 0.0003), as well as between NK and NK-T cells (p < 0.0019). There was instead no statistically significant correlation among the different SF or PB lymphocytes and the most relevant clinical or serological parameters. CONCLUSION: This study, analyzing the impairment of different subsets involved in non-MHC-restricted cytotoxicity, suggests that this component of the cell-mediated immune response seems to play a pivotal role in the development of PsA.

[Immunohistochemical analysis of the expression of main adhesion molecules and tumor necrosis factors in the synovial membrane of psoriatic arthritis]. / Analisi immunoistochimica dell'espressione delle principali molecole di adesione e dei fattori di necrosi tumorale a livello della membrana sinoviale nell'artrite psoriasica.

OBJECTIVE: To define the expression and pattern of the synovial distribution of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1 and of TNFalpha and TNFbeta cytokines in psoriatic arthritis (PsA), according to the synovitis duration. METHODS: Cryostatic sections of the synovial membrane tissue samples were stained for the different antibodies using a standard three-stage-immunoperoxidase-labeling technique. RESULTS: E-selectin grade of staining was higher in those patients with a shorter disease duration compared to longstanding synovitic specimens, as well as ICAM-1 expression. On the contrary a higher VCAM-1 positivity was mainly found in longstanding PsA patients. Anti-TNFalpha positivity was found almost in all the specimens with no difference among the two groups, while the intensity of anti-TNFbeta positivity was globally higher in longstanding cases. CONCLUSIONS: Different adhesion molecules may separately participate to the synovitic process in the different phases of PsA, leading to the hypothesis of their different involvement during the disease evolution. Moreover the upregulation of TNFalpha and TNFbeta gives evidence to their local proinflammatory effect within the synovium and to their role in perpetuating the PsA synovitis.

Interleukin-13 in systemic sclerosis: relationship to nailfold capillaroscopy abnormalities.

The aim of this study was to investigate whether interleukin-13 (IL-13) serum levels correlate to different nailfold capillaroscopy (NC) findings in patients with systemic sclerosis (SSc). IL-13 serum levels were measured using an ELISA method. The following NC abnormalities were considered: the presence of giant loops, haemorrhages, loss of capillaries, disorganisation of the vascular array, ramified/bushy capillaries and sludging of blood. A semiquantitative rating scale was adopted to score these changes, as well as a rating system for avascular areas and three morphological NC patterns ('early', 'active' and 'late'). Mean capillary density was determined by counting the total number of capillaries in a 1 mm length, and the arterial and venous diameters of the capillary as well as the total loop diameter were measured. In SSc patients IL-13 serum levels were significantly higher than in controls ( P < 00.1), whereas in patients with ( n=8) and without ( n=24) abnormal IL-13 serum levels (>17 pg/ml) the comparison of the NC features showed significantly relevant differences concerning a more frequent 'active' NC pattern ( P < 0.02), the presence of haemorrhages ( P < 0.0037) and sludging of blood ( P < 0.038), as well as larger total loop ( P < 0.036) and arterial ( P < 0.03) diameters, in those patients with elevated IL-13 serum levels. The study confirmed that IL-13 serum levels are higher in the sera of patients with SSc, and shows for the first time the significant correlations between this serological finding and some of the main relevant SSc capillaroscopic features, leading us to believe that this cytokine not only seems to sustain the immunological and fibrotic process of SSc, but might have a role in determining the more severe microvascular lesions in this disease.

Relationship of interleukin-12 and interleukin-13 imbalance with class-specific rheumatoid factors and anticardiolipin antibodies in systemic lupus erythematosus.

The aim of the study was to evaluate whether the imbalance between IL-12 and IL-13 serum levels, reflecting Th1/Th2 activity, is related to class-specific circulating rheumatoid factors (RF) and anticardiolipin (aCL) antibodies in SLE. Using ELISA we measured serum IL-12, IL-13, RF and aCL antibodies in 73 SLE patients and 20 healthy controls. The determination of IL-12/IL-13 ratio showed that IL-12 levels were above (group A), equal to (group B) or below (group C) IL-13 levels in 71.2%, 15.1% and 13.7% of SLE patients, respectively. IgM-RF levels were significantly higher in group C than in groups A ( P < 0.002) and B ( P < 0.019). Group C had also higher IgM-aCL levels than group A ( P < 0.04). No relationship between IL-12/IL-13 ratio and clinical or other laboratory parameters was found. It was concluded that the increased levels of both IgM-RF and IgM-aCL in patients with prevalent Th2 activity suggest that the predominance of Th2 over Th1 could drive autoantibody production in SLE patients.

Co-occurrence of psoriatic arthritis with collagenous colitis: clinicopathologic findings of a case.

A 58-year-old man developed psoriatic arthritis and, after 6 months, persistent watery diarrhoea. Biopsies from the colorectal mucosa showed thickened subepithelial collagen consistent with collagenous colitis. There also was an inflammatory cell infiltration (mainly lymphocytes and monocytes) in the chorion. These findings and the parallel course of articular and bowel complaints suggest a clinicopathologic correlation between arthritis and colic involvement.

[The role of interleukin-12 in immune-mediated rheumatic diseases]. / Il ruolo dell'Interleuchina-12 nelle malattie reumatiche a patogenesi immunitaria.

OBJECTIVE: IL-12 is a proinflammatory cytokine produced by different antigen presenting cells. It has been shown to exert a critical role in inducing Th1 phenotype, thus initiating cell-mediated immune responses, but the significance of IL-12 in rheumatic diseases is not clear. Aim of the study was to determine IL-12 serum levels in immune rheumatic diseases and to analyse the relationship of this cytokine with main clinical and laboratory parameters. METHODS: We analysed, by ELISA, serum IL-12 levels in 114 patients with SLE, 47 with SS, 32 with SSc, 84 with RA, 138 with PA and in 17 healthy controls. We also examined main clinical and laboratory parameters, including autoantibody profile and clinical indices of disease activity. RESULTS: IL-12 serum levels were significantly higher in SLE and SS patients respect to controls. IL-12 serum levels were significantly higher in SLE patients compared to those affected by RA, PA and SSc. When we evaluated disease activity in SLE patients, we found significantly higher IL-12 serum levels in subjects with fever or in those without renal involvement, while no correlation was found in the other rheumatic immune diseases. CONCLUSIONS: These findings suggest that IL-12, modulating cell and humoral immune responses, is involved in the pathogenesis of immune rheumatic diseases, such as SLE and SS.

Interleukin-13 in autoimmune rheumatic diseases: relationship with the autoantibody profile.

OBJECTIVE: Several cytokines play a role in the production of autoantibodies such as RF and ANA by B-lymphocytes; the role of IL-13 in this process has not been previously studied. We investigated the relationship between the serum concentration of this cytokine and circulating autoantibodies. METHODS: IL-13 serum levels, as well as RF and ANA, were evaluated in 282 patients with autoimmune rheumatic diseases including RA (n=84), SLE (n= 114), SS (n=52) and Scl (n=32). RESULTS: Serum levels of IL-13 (pg/ml) were significantly higher in patients with RA (p < 0.00003), SLE (p < 0.03), SS (p < 0.0007), or Scl (p < 0.025) compared to controls. IL-13 serum levels correlated with those of RF in RA (p < 0.00001), SLE (p < 0.003) and Scl (p < 0.03). IL-13 levels were higher in RA (p<0.0003), SLE (p<0.005) and Scl (p<0.05) patients with RF than in patients without RF. SS patients with antiSSA/Ro antibodies had significantly higher IL-13 levels than SS patients without this autoantibody (p < 0.04). No statistically significant correlation was found between IL-13 levels and any other antinuclear autoantibody, total immunoglobulin levels or the main clinicalfeatures of each disease. CONCLUSION: The evidence of higher IL-13 levels in our RA, SLE, SS and Scl patients confirms that this cytokine is involved in the pathogenesis of autoimmune rheumatic diseases. The relationship of this cytokine with RF in RA, SLE and Scl, as well as with antiSSA/ Ro antibody in SS, strengthens the hypothesis that it plays a role in autoantibody production. However, the different autoantibody synthesis by B-cells recognises different pathways depending on the underlying autoimmune disease.

Interleukin 13 in synovial fluid and serum of patients with psoriatic arthritis.

OBJECTIVES: To compare the pattern of interleukin (IL) 13 production in synovial fluid (SF) and serum of patients with psoriatic arthritis (PsA) with that in patients with rheumatoid arthritis (RA) and osteoarthritis (OA), investigating its relation to the proinflammatory cytokine IL12. METHODS: SF and serum IL13 levels were determined in 35 patients with PsA, 36 with RA, and 15 with OA. The main clinical and laboratory variables, including number of painful and/or swollen joints, Ritchie index, morning stiffness, erythrocyte sedimentation rate, level of C reactive protein, level of rheumatoid factor, and SF analysis, were also evaluated. RESULTS: SF IL13 levels were significantly higher in patients with PsA (p<0.02) or RA (p<0.012) than in patients with OA, with no significant difference between the former two. SF IL12 levels were significantly higher in patients with PsA (p<0.023) than in those with OA. Serum IL13 (p<0.0001) and IL12 (p<0.02) levels were lower in patients with PsA than in those affected by RA. Only patients with PsA had higher IL13 levels in SF than in serum (p<0.002). The IL13 SF/serum ratio was higher in the PsA group than in the group with RA (p<0.005) or OA (p<0.026). SF IL13 levels correlated with serum IL13 levels (p<0.0001) in RA and with SF IL12 levels (p<0.03) in PsA. CONCLUSIONS: In PsA, there appears to be localised production of IL13, in balance with IL12, in the inflamed joints. The distinct IL13 secretion profiles in PsA, RA, and OA may be related to the clinical pictures, reflecting the different pathogenic mechanisms involved in inflammatory and degenerative joint diseases.

[Anti-tissue transglutaminase antibodies in inflammatory and degenerative arthropathies]. / Anticorpi anti-transglutaminasi tissutale nelle artropatie a carattere infiammatorio e degenerativo.

Recent studies identified tissue transglutaminase (tTG) as the antigen eliciting antiendomysial antibodies (EMA) in celiac disease (CD). Anti-tTG antibodies have therefore been proposed as a serological test for CD. Nevertheless, IgA anti-tTG but not EMA have also been found in inflammatory bowel disease patients, suggesting that these antibodies are linked to a tissue lesion rather than to an auto-immune component of CD. To confirm this hypothesis, we evaluated the presence of IgA anti-tTG in patients with inflammatory and degenerative diseases, in whom tissue lesions presented far away from the intestinal mucosa. The study was carried out on the serum and synovial fluid (SF) of 68 patients with rheumatoid arthritis (RA=33), psoriatic arthritis (PsA=26) and osteoarthritis (OA=9). In RA, PsA and OA sera, IgA anti-tTG were positive in 33%, 42% and 11% of patients, respectively. Serum anti-tTG levels were significantly higher in RA (p<0.0001), PsA (p<0.0001) and OA (p<0.02) with respect to healthy controls. SF anti-tTG levels were significantly higher in PsA (p<0.018) than in OA. A good correlation between serum and synovial fluid anti-tTG levels was found in all arthropathies This study suggests that tTG is not the only antigen of EMA and, furthermore, that IgA anti-tTG antibodies represent a general lesion-associated event. Moreover, the significant correlation between serum and synovial fluid anti-tTG levels allow us to hypothesise that these antibodies could be synthesized in the site of arthritic lesions.

Soluble interleukin-2 receptor in Sjögren's syndrome: relation to main serum immunological and immunohistochemical parameters.

Our aim was to study sIL-2R relationship with main serum immunological and LSG immunohistochemical parameters, including surface antigen expression of immune activation, in 27 patients with primary SS. Serum sIL-2R levels were significantly higher in SS (p<0.00005), as well as in SLE (p<0.05) and RA (p< 0.000001) patients than in controls. In SS patients with abnormal slL-2R values (n = 7) we found higher levels of anti-SSB/La antibodies (p<0.05), IgM-RF (p<0.014) and CRP (p<0.003) with respect to those with normal sIL-2R values (n = 20). Moreover, sIL-2R levels correlated positively with those of anti-SSB/La antibodies (p<0.0037) and with CRP (p<0.008). The comparison of groups with (A) and without (B) abnormal slL-2R levels reveals a statistically different percentage of patients with foci number > 1 (86% vs 40%; p <0.047), and CD25 expression on lymphocytes (100% vs 40%; p < 0.008). The frequency (p < 0.025) of CD25 expression on lymphocytes was higher in group A than in group B. The frequency of CD25 expression on the infiltrates correlated not only with sIL-2R levels (p<0.047), but also with anti-SSB/La antibody values (p < 0.044), with Tarpley histological classes (p < 0.009) and with frequency of HLA-DR expression on lymphocytes (p<0.004) and on epithelial cells (p<0.002). The frequency of epithelial CD25 expression also correlated with that of epithelial HLA-DR (p<0.004). Our report suggests that slL-2R is linked to glandular involvement in primary SS.

Ultrasound measurements at the proximal phalanges in male patients with psoriatic arthritis.

Bone ultrasound parameters at the proximal phalanges of the hands were measured in 55 male patients with psoriatic arthritis (PA) (39 with peripheral radiologic involvement and 16 with axial involvement), comparing the findings with those in 16 rheumatoid arthritis (RA) patients, 20 ankylosing spondylitis (AS) patients and 55 age- and sex-matched normal controls. Mean values of amplitude-dependent speed of sound (Ad-SoS) and ultrasound bone profile score (UBPS) were significantly lower in RA (p < 0.001 and p < 1 x 10(-5)) and PA (p < 0.03 and p < 1 x 10(-6)) patients than in controls, while there was no statistically significant difference between AS patients and healthy subjects. Ultrasound parameters showed a significant negative correlation with age in all groups. In each patient group ultrasound values were unrelated either to disease duration or to inflammatory indices such as erythrocyte sedimentation rate and C-reactive protein. Moreover no significant differences were observed between ultrasound parameters of the dominant and the nondominant hand. PA patients with and without axial radiologic changes did not show any differences in ultrasound parameters. However, PA subjects with peripheral involvement only had significantly higher Ad-SoS (p < 0.04) and UBPS (p < 0.04) values than RA patients. PA patients with axial lesions had significantly lower (p < 0.04 and p < 0.01) ultrasound values than AS patients. These findings suggest that PA ultrasound techniques performed at the peripheral level are of value to speculate on bone involvement, although we think that ultrasound measurements cannot yet be recommended for monitoring bone involvement in these patients.

Immunohistologic markers of immune activation and changes of glycosylation of serum proteins in primary Sjögren's syndrome.

OBJECTIVE: [corrected] To assess the possible correlations between the immune activation of certain surface antigens at the lip salivary gland (LSG) level, and changes in glycosylation of serum proteins in primary Sjögren's syndrome (SS). METHODS: LSG biopsy samples were obtained from 22 SS patients (mean age 56.3 years; mean disease duration 70.8 months) and prepared for immunohistochemical analysis using murine monoclonal antibodies for interleukin-2 receptor (IL-2R) (CD25) and for the class II major histocompatibility antigen HLA-DR. The glycosylation of serum proteins was evaluated in all patients by an enzyme-linked lectin assay (ELLA) using concanavalin A (Con A). RESULTS: In LSG specimens the presence of IL-2R was observed at the infiltrating level, mainly periductally, in 13 (59%) cases and on the epithelial cells of 14 (64%) patients. In 13 out of 22 SS patients (59%) a marked positivity both of the infiltrates and of the epithelium was found for anti-HLA-DR monoclonal antibody. The degree of expression of different antigens on LSG samples was correlated with their histologic class according to Tarpley evaluation. The positivity for IL-2R and HLA-DR molecules on glandular tissues was correlated. A significant increase in the total Con A reactivity of serum proteins was found in those patients expressing IL-2R and HLA-DR antigens on LSG specimens. CONCLUSIONS: The co-expression of IL-2R and HLA-DR antigens on both the epithelium and infiltrates of LSG is consistent with a participation of these cells in the immune process of SS. Moreover, changes in the glycosylation of serum proteins seem to be related to the presence of these immunoactivation markers of the disease at the LSG level, suggesting that the control of protein glycosylation could be mediated by the same mechanisms involved in the tissue damage of SS.

Down-regulation of natural killer cells and of gamma/delta T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity?

A depletion of natural killer (NK) cells seems to play a role in the course of systemic lupus erythematosus (SLE) whereas the possible involvement in this disease of T cell receptor (TCR) gamma/delta positive T cells is still debated. The aim of this study was to evaluate the peripheral blood mononuclear cells (PBMCs) that express NK surface markers CD16 and CD56 or gamma/delta TCR antigen in 58 SLE patients, investigating the possible role of these cell subsets involved in non-MHC-restricted cytotoxicity and their relationship with the main clinical and laboratory parameters. SLE patients had, with respect to controls, considerably decreased values of NK cells (P<0.0004 in percentage and P<0.00004 as absolute number), of non-MHC-restricted T cytotoxic lymphocytes (P<0.007 and P<0.0015, respectively) and of T cells expressing gamma/delta TCR (P<0.02 and P<0.004, respectively). The absolute numbers of these cell subsets positively correlated to each other (P<0.009). gamma/delta T cells inversely correlated with higher ESR values, both percentually (P<0. 006; r=-0.367) and in absolute number (P<0.009; r=-0.350). Moreover, the percentage values of this cell subset inversely correlated with higher levels of CRP (P<0.05; r=-0.256) while SLE patients with anti-SSB/La antibodies had lower values of T lymphocytes bearing gamma/delta TCR, both as percentage (P<0.008) and as absolute number (P<0.02). Our study indicates that non-MHC-restricted cytotoxicity, shared by NK, NK-like and gamma/delta T cells, may be down-regulated in SLE patients, owing to a significant reduction of these PBMC subsets. These specific cell subset impairments seem to affect only some aspects of the disease, suggesting a weakening of the regulatory properties of these cells in the control of different immunological and inflammatory features of SLE, that could be of importance in its clinical expression.

Diastolic function abnormalities in rheumatoid arthritis. Evaluation By echo Doppler transmitral flow and pulmonary venous flow: relation with duration of disease.

OBJECTIVE: The aim of this study was to evaluate left ventricular filling in patients with rheumatoid arthritis (RA), analysing transmitral flow and pulmonary venous flow, with special regard to age and disease duration. METHODS: 32 patients affected by RA according to ARA criteria were selected, without evidence of cardiac disease, and compared with matched control subjects. All patients and the control group were submitted to M-mode, two dimensional, Doppler and colour Doppler (continuous and pulsed wave) echocardiography. The following diastolic parameters were evaluated: transmitralic flow (E/A ratio), pulmonary venous flow (S/D ratio), a-Pw, IVRT and DT. RESULTS: In RA patients left ventricular filling abnormalities were found characterised by a reduced E/A ratio (mean (SD) 1.16 (0.31) v. controls 1.37 (0.32); p = 0.02) and an increased S/D ratio (1.43 (0.40) v. controls 1.22 (0.29); p = 0.017). In the group of patients a relation was found between E/A ratio and disease duration (r= 0.40, p = 0.01 Spearman rank correlation). CONCLUSIONS: At present, it is concluded that RA patients, in absence of clinical evidence of heart disease, show diastolic dysfunction characterised by impaired E/A and S/D ratio. The relation between transmitral flow alteration and disease duration suggests a sub-clinical myocardial involvement.

Class specific rheumatoid factors and antiphospholipid syndrome in systemic lupus erythematosus.

The relationship of rheumatoid factors (RF) with antiphospholipid syndrome (aPLS) and anticardiolipin antibodies (aCL) has rarely been investigated in systemic lupus erythematosus (SLE). We found IgM-RF, IgG-RF, IgA-RF, IgM-aCL, IgG-aCL, IgA-aCL, respectively, in 35.4%, 35.4%, 33.8%, 23.1%, 23.1%, 20.0% of 65 SLE patients. Class specific RFs were negatively associated (P<0.05) with IgG-aCL. The frequency of definite or probable aPLS according to Alarcon-Segovia classification criteria was significantly (P<0.05) different (8.7% vs 30.9%) in patients with or without IgG-RF. Among the other clinical features of SLE, we found that patients with IgG-RF, compared to patients lacking this autoantibody, showed a lower frequency (P<0.05) of serositis (21.7% vs 52.4%) and hematologic (52. 2% vs 80.9%) disorders. The levels of IgG-RF and IgM-RF negatively correlated with the number of ARA criteria (P<0.05) but not with the indices of diseases activity or damage. Our study shows that in SLE the presence of RFs are not markers of severity of the disease, but the negative association between IgG-RF and IgG-aCL suggests a distinct role of these autoantibodies in the pathology of SLE, whereas the presence of IgG isotype may identify a subset of SLE patients having a lower risk to develop some clinical manifestations such as aPLS.