Anti-citrullinated peptides as autoantigens in rheumatoid arthritis—relevance to treatment

Abatacept for Rheumatoid Arthritis: A Novel Formulation, New Mechanisms, New Possibilities

“…Однако опре-деление АЦЦП (и в меньшей степени IgM РФ) имеет су-щественное значение не только для диагностики РА, но и для прогнозирования риска развития РА у здоровых людей [88] (они обнаруживаются в сыворотках пациен-тов более чем за 10 лет до первых симптомов РА) и транс-формации недифференцированного артрита (НДА) в РА [89]. Гиперпродукция АЦЦП (особенно в комбинации с РФ) ассоциируется с прогрессированием деструкции суставов [82,90], развитием экстраартикулярных (сис-темных) проявлений [82], повышением общей летально-сти, связанным с более частым развитием коморбидных состояний, в первую очередь, кардиоваскулярных ослож-нений [91,92], «резистентностью» или, напротив, «чув-ствительностью» к терапии теми или иными противовос-палительными препаратами [93]. В настоящее время вы-деляют два основных клинико-лабораторных субтипа РА: АЦЦП-позитивный и АЦЦП-негативный.…”

Vaccine development for rheumatoid arthritis

“…In that regard, most notably, autoantibodies directed against CCP protein/peptides (ACPA) were found in the sera of about 70% of RA patients as well as in the sera of individuals who eventually developed RA. In many of these cases ACPAs were found in these sera several years prior to the appearance of RA clinical symptoms [32]. These novel discoveries resulted in a new venture suggesting that prophylactic vaccination might be the long sought after "cure" for RA.…”

“…The evidence for this appears to be substantial and compelling since ACPAs were demonstrated to induce several critical components of RA pathology. These included the production of TNF-α by activated macrophages, enhanced differentiation of osteoclasts, IL-8, a pro-inflammatory biomarker of inflammation, as well as having the capacity to induce complement activation [32]. All of these factors promote synovial joint progression of disease typical of RA.…”

“…Thus, recent evidence has shown that cyclic citrullinated proteins (CCP) were likely to be the arthritogenic proteins which are the critical protein component for developing RA [32]. In that regard, most notably, autoantibodies directed against CCP protein/peptides (ACPA) were found in the sera of about 70% of RA patients as well as in the sera of individuals who eventually developed RA.…”

Adduct Formation and Context Factors in Drug Hypersensitivity: Insight from Proteomic Studies

“…In certain autoimmune diseases, proteins suffer posttranslational modifications that render them immunogenic. For instance, citrullinated peptides from several endogenous proteins, including extracellular and intracellular proteins like vimentin, alphaenolase and histones, act as antigens to which auto-antibodies are detected in several inflammatory diseases, like arthritis [4,5]. Moreover, carbamylated and acetylated vimentin are also recognized by autoantibodies from patients [6].…”