Systemic sclerosis sine scleroderma should be included in the spectrum of SSc with limited cutaneous involvement and should not be considered a distinct or separate disorder.

Objective To evaluate clinical associations of anti-PM/Scl antibodies in patients with Systemic Sclerosis (SSc) in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (SRC), malignancies, and functional outcome of interstitial lung disease (ILD). Methods (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared to 7,202 anti-PM/Scl-, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case-control study: additional data were collected for 165 anti-PM/Scl+ SSc (85 from the EUSTAR registry), and compared to 257 anti-PM/Scl- SSc controls, matched for sex, cutaneous subset, disease duration, and age at SSc onset. Results Patients with isolated anti-PM/Scl positivity, as compared with anti-Pm/Scl-, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of dermatomyositis, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed. Conclusion The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous dermatomyositis, calcinosis, and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.

To evaluate demographic, clinical and laboratory features associated with scleroderma-specific auto-antibodies. Sera of 100 patients with systemic sclerosis (SSc) were analyzed by an indirect immunofluorescence technique with HEp-2 cells as a substrate. Specific ANA such as anti-centromere antibodies (ACA), anti-topoisomerase (TOPO), anti-RNA polymerase III (Pol 3), anti-U3-RNP (U3-RNP), anti-Th/To (Th/To) and anti-PM/Scl (PM/Scl) were detected by line immunoassay and anti-U1-RNP (U1-RNP) by ELISA. Frequency of clinical features associated with a specific antibody group was reported cumulatively over the follow-up period. Frequency of specific clinical features was compared across the two disease subtype including limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) as well as the auto-antibody groups. Ninety-four percent of patients were ANA positive with significant higher skin score, Raynauds and digital ulcer/gangrene. Anti-TOPO was detected in 71% of all patients, in 90.5% of dcSSC and in 65.8% of lcSSc. Anti-TOPO was significantly associated with dcSSc, higher skin score, digital ulcer/gangrene, pulmonary fibrosis, DLCO <70%. U1-RNP antibody was associated with lower fibrosis in lung. ACA was positive in 7% of patients and exclusively in those with lcSSc. We did not find association between gender and presence of auto-antibodies. Anti-TOPO antibody had a high prevalence in contrast to low prevalence of ACA antibody. There were no differences in clinical subtypes of the disease in patients with positive anti-TOPO and positive ACA. Differences in prevalence of auto-antibodies are suggestive of further genetic study.

Contribution of killer cell immunoglobulin-like receptors (KIR) and their human leucocyte antigen (HLA) class I ligands in the pathogenesis of autoimmune diseases has been shown in several studies. In this study, the possible association of KIR genes, their known HLA ligands and compound KIR/HLA genotypes with ankylosing spondylitis (AS) was assessed. Combined KIR/HLA ligand genotyping was performed by a polymerase chain reaction-sequence-specific primers assay in 35 Iranian patients with AS, and genotypes were compared to those in 200 healthy individuals. The frequencies of telomeric cluster genes KIR2DL5A, KIR2DS1 and KIR3DS1 were significantly increased in AS patient group (P(c) = 0.0082, P(c) = 0.0195 and P(c) = 0.0328, respectively). Conversely, HLA-Bw4 ligand (the presence of one or more -B Bw4(Ile80) , -B Bw4(Thr80) and -A Bw4 epitopes) (P(c) = 0.0004) and HLA-B Bw4(Ile80) (P(c) = 0.053) were less frequent in these patients. Meanwhile, compound KIR/HLA genotype analyses revealed lower frequency of KIR3DL1+HLA-B Bw4(Ile80) (P(c)  = 0.0343) and higher frequency of KIR2DS1+HLA-C2 (P(c) = 0.0308) combinations in patients with AS than in controls. In addition, the genotypes iKIR+HLA > aKIR+HLA (P(c) = .0308) and iKIR+HLA > aKIR (P(c) = 0.0258) were statistically less common, and genotypes iKIR+HLA = aKIR+HLA (P(c) = 0.0081) and iKIR+HLA < aKIR (P(c) = 0.077) were more common in patient group. Our findings suggest a role for excessive or inappropriate NK cell activation through 'KIR/HLA' system in AS disease.