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Objectives: To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial SpondyloARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting., Methods: QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of SpondyloArthritis international Society criteria for axSpA., Results: Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1±13.3 years at axSpA symptoms onset and 39.5±13.0 years at diagnosis. Of the patients, 51.4% presented with ≥1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup., Conclusions: QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.

Conclusive data about the prevalence of endothelial dysfunction and atherosclerotic process in ankylosing spondylitis (AS) patients with respect to the general population are lacking. Elevated plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been reported in clinical conditions associated with endothelial dysfunction and atherosclerotic disease. We performed a cross-sectional study to evaluate plasma ADMA levels and atherosclerotic disease in AS patients. Seventeen consecutive AS patients free of any cardiovascular disease and 17 healthy controls [strictly matched for sex, age (±5 years) and atherosclerotic risk factors] were recruited. Plasma ADMA levels were assessed by capillary electrophoresis. Common carotid artery intima-media thickness (CCA-IMT), flow-mediated dilatation (FMD) and arterial stiffness (aS) were registered as surrogate markers of atherosclerotic disease. Plasma ADMA levels appeared significantly (p = 0.001) higher in AS patients (0.65 ± 0.10 μmoli/L) than in the control subjects (0.54 ± 0.07 μmoli/L) while no statistically significant differences between AS and controls were demonstrated in CCA-IMT, FMD, and aS. AS patients showed increased plasma ADMA levels with respect to control subjects. On the contrary, we were not able to document a significant difference in atherosclerotic process between patients and controls.

Objective: To compare haplotype distribution in HLA-B27-positive patients with ankylosing spondylitis (AS) and healthy control subjects possessing either AS-associated HLA-B27 alleles or the non-AS-associated HLA-B*2709 allele., Methods: DNA samples from 47 HLA-B27-positive patients with AS and 76 HLA-B27-positive healthy controls (19 positive and 57 negative for B*2709) living in different areas of Sardinia were collected and typed for HLA class I and class II alleles. The third exon of the B27 gene was analyzed for the presence of Asp(116) or His(116), which differentiates B*2709 from the other two B27 subtypes (B*2705 and B*2702) that are mostly found in Sardinia. The parents of 6 subjects positive for B*2709 were also typed for HLA class I and class II alleles. Statistical analysis was performed by Fisher's exact test., Results: In Sardinia, the B27 alleles conferring susceptibility to AS appear to be more frequently carried by a haplotype (A2;B27;Cw2;DR16) that reaches its highest frequency in patients with AS (A2 80.8%, B27 100%, Cw2 83%, and DR16 74.5%). Conversely, the non-AS-associated B*2709 allele is more frequently found together with other HLA alleles whose frequencies are inversely correlated with the disease (A32 or A30, Cw1, and DR12). Familial analysis of 6 subjects positive for HLA-B*2709 confirmed the existence of a "Sardinian" haplotype that is not associated with AS (A32;B*2709;Cw1;DR12)., Conclusion: In Sardinia, 2 distinct haplotypes harbor the non-AS-associated HLA-B*2709 allele or the AS-associated B27 alleles. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 may play some role in conferring susceptibility to AS.

Objective: In B27 transgenic rats, susceptibility to the development of a spondyloarthropathy-like disease has been shown to correlate with the level of B27 transgene expression on lymphoid cells. The aim of this work was to study HLA-B27 molecule expression in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) and from normal controls (NC)., Methods: Twenty B27(+) AS patients and 16 B27(+) NC were studied. HLA-B27 whole molecules and free heavy chains (HCs) and total HLA class I molecules were evaluated at the surface of PBMCs by immunofluorescence and flow cytometry. B27 subtypes were defined with the PCR-SSP (polymerase chain reaction-sequence-specific primer) technique. Cellular activation was evaluated by the expression of CD69, CD25 molecules and interferon gamma (IFN-gamma) production., Results: B27 expression was 55,536.3+/-18,961.0 MESF (molecules of equivalent soluble fluorochromes) units in AS and 25,936.0+/-12,117.5 MESF in NC (P=0.00009), total HLA class I expression was 448,840.2+/-136,293.8 MESF in AS and 533,494.4+/-232,931.1 MESF in NC (not significant), HC expression was 10,593.4+/-6,396.1 MESF in AS and 14,843.0+/-7,544.2 MESF in NC (not significant). The higher B27 expression in the SA group was not due to higher cell activation as it was not correlated with CD69 and CD25 expression in PBMCs or with the level of IFN-gamma. HLA-B27 expression did not correlate with indexes of disease status [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI)]., Conclusions: We found greater expression of HLA-B27 molecules in patients with AS than in healthy subjects. This phenomenon was not accompanied by general up-regulation of HLA class I molecules or by greater expression of classical T-cell activation markers. On this basis we propose that the higher expression of the HLA-B27 molecules is a further predisposing factor for the development of AS.

Ankylosing Spondylitis (AS) is characterised by the strongest association with an HLA antigen ever described for any disease. It represents therefore the ideal model for the understanding of the link between immune-mediated diseases and the HLA system. The role of HLA-B27 in the pathogenesis of AS will be discussed focusing on the recently described higher expression of these molecules in patients with AS compared with healthy controls.

Objective: We investigated the distribution of MICA triplet repeat polymorphism in a random population and in patients with seronegative spondyloarthritis from Sardinia compared to continental Italy., Methods: We analyzed the distribution of MICA triplet repeat polymorphism in HLA-B*2709 [not associated with ankylosing spondylitis (AS)] and B*2705 (associated with AS) haplotypes, to verify whether the strong association of MICA-A4 with HLA-B27 reported in other populations is maintained in Sardinia, and compared the distribution of MICA-A alleles in HLA-B27 negative versus HLA-B27+ patients with AS., Results: We found that the frequency of MICA-A4 triplet repeat allele in a random Sardinia population is higher (53.2%) than in other Caucasian populations (around 20%); this allele is strongly associated with both HLA-B*2709 and B*2705. No significant difference between HLA-B27+ patients with AS and healthy controls was found: the MICA-A4 allele was present in more than 90% of subjects. MICA-A4 was found in 16 out of 20 HLA-B27 negative Sardinian patients with AS, with a frequency (80%) more similar to that of the HLA-B27+ group of patients than that of controls., Conclusion: The high frequency of MICA-A4 allele in HLA-B27 negative patients with AS from Sardinia, suggests the presence within the HLA region of a susceptibility factor other and certainly weaker than B27. This factor is likely to be more easily found by analyzing genetically homogeneous populations like the Sardinian, characterized by a small number of very frequent haplotypes.

Diffuse idiopathic skeletal hyperostosis (DISH) is a well-described disorder of middle-aged people, with a unique spinal pathology characterized by calcification and ossification of the antero-lateral aspect of at least four contiguous vertebral bodies, with the sparing of intervertebral spaces and sacroiliac joints. DISH has rarely been reported associated with ankylosing spondylitis (AS), a chronic inflammatory articular disease most commonly involving the spine and sacroiliac joints. A 63-year-old man with clinical and radiological findings of DISH with associated AS is described here. The authors conclude that these two diseases may, albeit rarely, coexist.