Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis.

OBJECTIVE: To examine the potential of circulating cytokines and chemokines as biomarkers of cancer mortality risk in patients with rheumatoid arthritis (RA). METHODS: Male participants in the Veterans Affairs RA registry were followed up from the time of enrollment until death or December 2013. Cytokines and chemokines were measured in banked serum obtained at the time of enrollment, using a bead-based multiplex assay, and a previously developed cytokine score was calculated. Vital status and cause of death were determined through the National Death Index. Associations of cytokines with cancer mortality were examined using multivariable competing-risks regression. RESULTS: Among 1,190 men with RA, 60 cancer deaths (30 of which were attributable to lung cancer) occurred over 5,307 patient-years of follow-up. The patients had a mean age of 64.5 years, had established disease (median duration 8.7 years), were seropositive for rheumatoid factor (81%) or anti-cyclic citrullinated peptide antibody (77%), and frequently had a history of smoking (82% current or former). Seven of 17 analytes examined were individually associated with cancer mortality. The cytokine score was associated with overall cancer (subhazard ratio [SHR] 1.42, 95% confidence interval [95% CI] 1.08-1.85) and lung cancer (SHR 1.86, 95% CI 1.57-2.19) mortality in multivariable analyses. Those in the highest quartile of cytokine scores had a >2-fold increased risk of overall cancer mortality (P = 0.039) and a 6-fold increased risk of lung cancer mortality (P = 0.028) relative to the lowest quartile. A synergistic interaction between current smoking and high cytokine score was observed. CONCLUSION: Serum cytokines and chemokines are associated with cancer and lung cancer mortality in men with RA, independent of multiple factors including age, smoking status, and prevalent cancer.

An animal model of chronic rheumatic valvulitis induced by formalin-killed streptococci.

Rheumatic heart disease is the most severe complication of rheumatic fever. Till date, very few successful animal models of rheumatic valvular disease have been reported. This study aimed at developing a suitable animal model of chronic rheumatic valvulitis for further investigation and prevention of rheumatic heart disease. Lewis rats were immunized with one administration of formalin-killed and sonicated group A streptococci together with Complete Freund's Adjuvant every 7 days for three cycles followed by group A streptococci alone till killing. Control rats were administered adjuvants and saline. Rats in group 1 were killed 12 weeks after the initial injection. Rats in group 2 and control group were killed 24 weeks after the initial injection. Results 62.5% (5/8) of rats in group 1 developed myocarditis and 50% (4/8) developed valvulitis. Histological examination of cardiac sections showed only cellular infiltrates. In contrast, 75% (6/8) of rats in group 2 developed rheumatic-like myocarditis and 62.5% (5/8) developed chronic valvulitis. Histological manifestations of the hearts in group 2 animals involved not only acute damage such as cellular infiltrates, Aschoff-like cells, verrucous vegetation, but also chronic lesions such as fibrosis, vascular neogenesis. None of the rats (0/8) in control group presented myocarditis or valvulitis. Lewis rat repeatedly immunized with formalin-killed GAS may be a suitable animal model of chronic rheumatic valvulitis. It may be useful for future investigation of the pathogenesis and possible preventive strategies of human rheumatic heart disease.

NERDS syndrome: an additional case report.

NERDS is an eosinophilic disorder recently described by Butterfield and characterized by an association of nodules, eosinophilia, rheumatism, dermatitis and swelling. We describe an additional case, the third, of this new eosinophilic syndrome. The cardinal features included joint and cutaneous manifestations with prominent para-articular nodules and rheumatism, xerosis, recurrent urticarial eruption with angioedema associated with tissue and peripheral blood eosinophilia. A drug-induced (diclofenac) allergic rash and lymphadenopathy appeared during the course of the illness. Persistent leukocytosis with a maximum of 65% of eosinophils, mostly exhibiting the hypodense phenotype (activation index), was always present. During the acute phase of the disease, flow-cytometric analysis of blood and bone marrow revealed proliferation of activated CD4+/OKDR+ T helper cells and CD25+/OKDR+ eosinophils.

Extra-articular manifestations are uncommon in southern Chinese with rheumatoid arthritis.

Rheumatoid arthritis is characterized by both articular and extra-articular manifestations. Few studies have addressed the prevalence of extra-articular manifestations in non-Caucasoid races. We have studied 153 Southern Chinese patients with RA and found that such features are uncommon when compared with previous reports in Caucasoids. The only extra-articular manifestations were rheumatoid nodules which were present in 4.6%, and episcleritis and cutaneous vasculitis in 0.7% each. A further 12.4% had mild sicca symptoms. These findings were in direct contrast with the severity of articular disease as 73% of patients had erosive disease which was graded as severe in 37%. The reason for the low prevalence of extra-articular manifestations is not known but may be due, in part, to the rarity of the HLA-DR4 subtype, HLA-Dw4 in the Southern Chinese population.

The prevalence and distribution of macrophages bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in synovium.

Fc-receptors for IgG (Fc gamma R) are important triggers of effector function in macrophages. We have investigated the distribution of cells bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in 14 synovia and 3 nodules from rheumatoid arthritis (RA) patients, using monoclonal antibodies on serial cryostat sections. 8 osteoarthritis (OA), 2 ankylosing spondylitis (AS) patients and one sarcoid patient were also studied. Significant numbers of macrophages bearing Fc gamma R were present in inflamed synovial tissue with no significant difference in relative frequency between RA and OA. There was no correlation with the degree of lymphocytic infiltration. Distinctive staining patterns for the three Fc-receptors suggest differential regulation of these molecules on macrophages in synovium.

Immunofluorescence studies of florid rheumatic Aschoff lesions.

We studied cardiac tissues of a patient who died of severe rheumatic myocarditis. Multiple Aschoff lesions were present throughout both ventricles and auricles. Immunofluorescence studies showed large monocytoid cells staining with OKM1 and anti-Leu M-3 as well as anti-Ia. Scattered T cells in areas of focal myocarditis stained with OKT3. Parallel staining for cardiac myosin-heavy chain antigens showed patchy dissolution of cardiac muscle fibers and traces of cardiac myosin within large monocytoid Aschoff cells.