Alfonso Massara

Central nervous system involvement in Sjögren’s syndrome: unusual, but not unremarkable—clinical, serological characteristics and outcomes in a large cohort of Italian patients

OBJECTIVES To perform an observational retrospective cross-sectional case-control study to evaluate prevalence, clinical patterns and outcomes of CNS involvement in a large cohort of primary SS (pSS) patients. METHODS A total of 424 pSS patients, diagnosed according to the 2002 criteria proposed by the American-European Consensus Group, were checked for CNS involvement after exclusion of secondary causes. Demographic, clinical, seroimmunological data were compared between patients with and without CNS involvement. Neuroimaging data were also analysed. RESULTS CNS involvement was detected in 25 (5.8%) patients (24 females and 1 male) both at disease onset (52%) and later (48%) with a mean latency after diagnosis of 7 years. Diffuse (40%), focal/multifocal (36%), multiple sclerosis (MS)-like disease (20%) and isolated optic neuritis (4%) were the most common CNS clinical pictures. Disease duration, lung involvement and decreased C(4) were associated with CNS involvement, while articular manifestations were more frequently observed in patients without neurological complications. Most cases had an acute, often recurrent course with spontaneous remission or only mild neurological impairment. CONCLUSIONS CNS involvement represents a rare but not negligible complication of pSS, which may occur with a bimodal temporal pattern, both at onset and later, prompting attention in the differential diagnosis of apparently isolated neurological syndromes. Lung involvement emerged as the strongest risk factor for CNS involvement with a relative risk of 7.9, along with disease duration and decreased C(4).

SAPHO syndrome and infections

The syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) encompasses a broad spectrum of cutaneous manifestations associated with osteitic and hyperostotic lesions, which typically may involve the anterior chest wall (ACW). The aetiopathogenetic mechanisms as well as the nosographic framing of the disease are still not fully defined although an important role has been suggested for Propionibacterium acnes (P. acnes). This germ might be able to stimulate both the innate and the T-cell-mediated immune system. The elicited immunological response could be an attempt to eliminate the germ thus inducing the perpetuation of the inflammation. Whether the osteo-articular changes seen in SAPHO could be attributable directly to the infection or to an inflammatory reaction induced by pathogenic material remains a debated issue. The current concept of SAPHO syndrome as a reactive infectious osteitis in genetic predisposed subjects seems appealing, but it has not been yet demonstrated.

Normalization of A2A and A3 adenosine receptor up-regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

OBJECTIVE To investigate A(1), A(2A), A(2B), and A(3) adenosine receptors in lymphocytes and neutrophils from patients with early rheumatoid arthritis (ERA) as well as from RA patients treated with methotrexate (MTX) or anti-tumor necrosis factor alpha (anti-TNFalpha), as compared with those in age-matched healthy controls, and to examine correlations between the status and functionality of adenosine receptors and TNFalpha release and NF-kappaB activation. METHODS Adenosine receptors were analyzed by saturation binding assays and Western blot analyses. We investigated the potency of typical A(2A) and A(3) agonists in the production of cAMP in control subjects, ERA patients, and RA patients treated with MTX or anti-TNFalpha. In a separate cohort of RA patients, TNFalpha release and NF-kappaB activation were evaluated in plasma and nuclear extracts, respectively. RESULTS In ERA patients, we found a high density and altered functionality of A(2A) and A(3) receptors. The binding and functional parameters of A(2A) and A(3) receptors normalized after anti-TNFalpha, but not MTX, treatment. TNFalpha release was increased in ERA patients and in MTX-treated RA patients, whereas in anti-TNFalpha-treated RA patients, release was comparable to that in the controls. NF-kappaB activation was elevated in ERA patients and in MTX-treated RA patients. Anti-TNFalpha treatment mediated decreased levels of NF-kappaB activation. CONCLUSION A(2A) and A(3) receptor up-regulation in ERA patients and in MTX-treated RA patients was associated with high levels of TNFalpha and NF-kappaB activation. Treatment with anti-TNFalpha normalized A(2A) and A(3) receptor expression and functionality. This new evidence of A(2A) and A(3) receptor involvement opens the possibility of exploiting their potential role in human diseases characterized by a marked inflammatory component.