Background: Systemic sclerosis (SSc), one of the most complex connective tissue disease, is characterized by three pathogenic events namely, vascular damage, autoimmunity and fibroblast activation, leading to a widespread fibrosis of skin and internal organs (1,2). Previous studies showed that 1) carbamylation mainly affects structural proteins undergoing to a low turn-over rate, namely dermal skin and tendons-associated proteins; and that 2) carbamylated proteins accumulate in skin in an age-dependent manner, contributing to tissue alteration (3). Objectives: As dermis is a disease target and anti-carbamylated protein antibodies (anti-CarP Ab) have been reported in patients with SSc (4), we sought to evaluate any relationship between anti-CarP Ab and clinical parameters reflecting skin involvement in SSc. Methods: Serum samples and clinical data from 123 patients with SSc were collected. Anti-CarP Ab were detected by indirect ELISA, using carbamylated bovine serum albumin as the antigen. Serum Anti-CarP Ab levels were also measured in 41 healthy aged-matched individuals. Clinical data were retrieved as previously reported (5). Results: The mean serum levels of anti-CarP Ab did not statistically differ between healthy and SSc group. In SSc, Spearman analysis showed that anti-CarP inversely correlated with the modified Rodnan skin score (RSS) (R= -0.325, p<0.001), independently of patients' age. Receiver operating characteristics (ROC) analysis identified the anti-CarP cutoff that best discriminated dichotomized clinical variables related to skin involvement. This cutoff that was employed to subdivide SSc patients into anti-CarP positive and anti-CarP negative patients. Three SSc skin-related clinical parameters were significantly different between groups: RSS (p=0.001), SI skin (p=0.002), and scleredema (p<0.001). A worse skin involvement was associated with low anti-CarP levels. Conclusions: The study shows that anti-CarP Ab serum level inversely associates to the severity of skin involvement in SSc patients. One possible mechanism to explain the inverse association is that the disease-dependent accumulation of carbamylated proteins in the skin may neutralize circulating anti-CarP Ab, thus contributing to their serum levels decrease. However, further investigation is needed to clarify this issue and to assess whether the levels anti-CarP Ab can be useful in the clinical setting of SSc.
ANTI-CARBAMYLATED PROTEIN ANTIBODIES IN PATIENTS WITH SYSTEMIC SCLEROSIS: AN INTRIGUING ASSOCIATION WITH SKIN INVOLVEMENT
M. Prete;A. corrado;F. P. Cantatore;F. Perosa
2017-01-01
Abstract
Background: Systemic sclerosis (SSc), one of the most complex connective tissue disease, is characterized by three pathogenic events namely, vascular damage, autoimmunity and fibroblast activation, leading to a widespread fibrosis of skin and internal organs (1,2). Previous studies showed that 1) carbamylation mainly affects structural proteins undergoing to a low turn-over rate, namely dermal skin and tendons-associated proteins; and that 2) carbamylated proteins accumulate in skin in an age-dependent manner, contributing to tissue alteration (3). Objectives: As dermis is a disease target and anti-carbamylated protein antibodies (anti-CarP Ab) have been reported in patients with SSc (4), we sought to evaluate any relationship between anti-CarP Ab and clinical parameters reflecting skin involvement in SSc. Methods: Serum samples and clinical data from 123 patients with SSc were collected. Anti-CarP Ab were detected by indirect ELISA, using carbamylated bovine serum albumin as the antigen. Serum Anti-CarP Ab levels were also measured in 41 healthy aged-matched individuals. Clinical data were retrieved as previously reported (5). Results: The mean serum levels of anti-CarP Ab did not statistically differ between healthy and SSc group. In SSc, Spearman analysis showed that anti-CarP inversely correlated with the modified Rodnan skin score (RSS) (R= -0.325, p<0.001), independently of patients' age. Receiver operating characteristics (ROC) analysis identified the anti-CarP cutoff that best discriminated dichotomized clinical variables related to skin involvement. This cutoff that was employed to subdivide SSc patients into anti-CarP positive and anti-CarP negative patients. Three SSc skin-related clinical parameters were significantly different between groups: RSS (p=0.001), SI skin (p=0.002), and scleredema (p<0.001). A worse skin involvement was associated with low anti-CarP levels. Conclusions: The study shows that anti-CarP Ab serum level inversely associates to the severity of skin involvement in SSc patients. One possible mechanism to explain the inverse association is that the disease-dependent accumulation of carbamylated proteins in the skin may neutralize circulating anti-CarP Ab, thus contributing to their serum levels decrease. However, further investigation is needed to clarify this issue and to assess whether the levels anti-CarP Ab can be useful in the clinical setting of SSc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
