Can CCL2 serum levels be used in risk stratification or to monitor treatment response in systemic sclerosis?

OBJECTIVE: The chemokine CCL2 has been consistently found to be up-regulated in systemic sclerosis. To explore the potential value of serum CCL2 measurement in disease assessment, we have compared CCL2 levels with clinical phenotype and investigated effect of therapy on circulating CCL2. METHODS: Serum samples from a well characterised cohort of 94 systemic sclerosis (SSc) patients, 16 patients with primary Raynaud phenomenon and 11 healthy controls were examined by ELISA. Our cohort of patients included 50 patients with limited cutaneous (lc)SSc (20 with lcSSc alone and 30 with pulmonary arterial hypertension-lcSSc), and 44 with diffuse cutaneous (dc)SSc, 30 of which had early-onset dcSSc. RESULTS: Serum levels of CCL2 were increased in both major SSc subsets. In early stage dcSSc 18/30 (60%) cases demonstrated markedly elevated CCL2, and this was associated with anti-topoisomerase or anti-RNA polymerase I/III antibody reactivity, and with greater frequency of major organ-based complications. Elevation of CCL2 serum levels in the lcSSc subset was not associated with pulmonary arterial hypertension, although there was a trend for reduction following treatment with prostacyclin analogues or bosentan. CONCLUSION: These findings suggest that the CCL2/CCR2 axis is a potential therapeutic target in SSc, particularly in the early dcSSc subset. CCL2 measurement may be useful for risk stratification in early stage disease, but its value in disease monitoring is questionable.

Angiographically proven coronary artery disease in scleroderma.

OBJECTIVE: It has been suggested that macrovascular disease is more common in patients with scleroderma (SSc). We investigated the prevalence of coronary artery disease (CAD) in SSc using coronary angiography. METHODS: Coronary angiography was performed in 172 patients with SSc and suspected CAD to examine the prevalence of significant CAD. The prevalence of CAD was estimated in the whole group and also according to age, gender and type of symptoms (typical angina, atypical angina and non-anginal pain or breathlessness). Standardized prevalence ratios (SPRs) were calculated in each symptomatic group in order to compare CAD rates amongst our observed population with those predicted using the Diamond and Forrester (D & F) probability analysis. This analysis provides an estimate of the probability of CAD based on gender, age and symptoms in subjects aged between 30-69 yrs. RESULTS: The observed prevalence of CAD in the whole population was 22% (38/172); 17% (6/36) in males and 23% (32/136) in females. A total of 41 patients were excluded because they were outside the age range for D & F analysis. Compared with the reference population, the SPRs for CAD in the three SSc groups were: 47% (95% CI 21.7-89.9) in the typical angina group (22 patients), 50% (95% CI 13.6-128) in the atypical angina group (22 patients) and 93% (95% CI 49.4-158.8) in the non-anginal pain or breathlessness group (87 patients). CONCLUSION: The prevalence of CAD in patients with SSc is similar and not greater to that expected in individuals without SSc.

Serial circulating adhesion molecule levels reflect disease severity in systemic sclerosis.

Microvascular damage occurs in systemic sclerosis (SSc) and is associated with increased expression of endothelial adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Elevated levels of the soluble circulating forms of these molecules have recently been reported in SSc. We have extended this observation by collecting serial serum samples from 12 patients with systemic sclerosis, at intervals between 4 and 12 months, through the course of their disease (mean period of observation 44 months). Circulating ICAM-1, VCAM-1 and E-selectin were measured by ELISA, and changes in these levels were compared with alterations in disease activity as assessed by skin sclerosis score, serum creatinine, erythrocyte sedimentation rate and pulmonary function tests coincident with each serum sample. The mean levels were ICAM-1 627 ng/ml, VCAM-1 959 ng/ml and E-selectin 81 ng/ml. In 8/12 patients, there was a substantial change in at least one disease parameter during the assessment period. In seven (88%) of these patients, changes in circulating VCAM-1 or E-selectin were associated with disease severity, falling with improvement in renal function or skin score, and rising with deterioration in pulmonary function tests. The maximum recorded level of VCAM-1 (3550 ng/ml) shortly preceded an acute renal SSc crisis. In two cases (25%), the correlation was statistically significant (P < or = 0.01). The ICAM-1 level did not reflect clinical changes in any patients. These results provide further evidence for endothelial cell dysfunction in SSc, and suggest that serial measurements of VCAM-1 and E-selectin may have potential value as surrogate markers for clinical progression or remission in this disease.

Characterization of cryoglobulins: some remarks on methodology.

OBJECTIVE: The experience of our group in the characterization of the cryoglobulins during the last 8 years is reported, and the possible advantages of immunofixation versus immunoblotting are discussed. METHODS: 25 out of 171 cryoprecipitates studied by immunofixation were also examined by immunoblotting, a technique which has been suggested to offer advantages in analysing monoclonal components. RESULTS: We confirm that immunofixation may be the technique of choice given its easier execution and interpretation, better standardization, and lower overall cost.