Study of Plasma Anti-CD26 Autoantibody Levels in a Cohort of Treatment-Naïve Early Arthritis Patients.

In rheumatoid arthritis (RA), the identification of biomarkers to adjust treatment intensity and to correctly diagnose the disease in early stages still constitutes a challenge and, as such, novel biomarkers are needed. We proposed that autoantibodies (aAbs) against CD26 (DPP4) might have both etiological importance and clinical value. Here, we perform a prospective study of the potential diagnostic power of Anti-CD26 aAbs through their quantification in plasmas from 106 treatment-naïve early and undifferentiated AR. Clinical antibodies, Anti-CD26 aAbs, and other disease-related biomarkers were measured in plasmas obtained in the first visit from patients, which were later classified as RA and non-RA according to the American College of Rheumatology criteria. Two different isotype signatures were found among ten groups of patients, one for Anti-CD26 IgA and other for Anti-CD26 IgG and IgM isotypes, both converging in patients with arthritis (RA and Unresolved Undifferentiated Arthritis: UUA), who present elevated levels of all three isotypes. The four UUA patients, unresolved after two years, were ACPA and rheumatic factor (RF) negatives. In the whole cohort, 51.3% of ACPA/RF seronegatives were Anti-CD26 positives, and a similar frequency was observed in the seropositive RA patients. Only weak associations of the three isotypes with ESR, CRP and disease activity parameters were observed. Anti-CD26 aAbs are present in treatment-naïve early arthritis patients, including ACPA and RF seronegative individuals, suggestive of a potential pathogenic and/or biomarker role of Anti-CD26 aAbs in the development of rheumatic diseases.

Calcineurin and Systemic Lupus Erythematosus: The Rationale for Using Calcineurin Inhibitors in the Treatment of Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a broad spectrum of clinical presentations that can affect almost all organ systems. Lupus nephritis (LN) is a severe complication that affects approximately half of the systemic erythematosus lupus (SLE) patients, which significantly increases the morbidity and the mortality risk. LN is characterized by the accumulation of immune complexes, ultimately leading to renal failure. Aberrant activation of T cells plays a critical role in the pathogenesis of both SLE and LN and is involved in the production of inflammatory cytokines, the recruitment of inflammatory cells to the affected tissues and the co-stimulation of B cells. Calcineurin is a serine-threonine phosphatase that, as a consequence of the T cell hyperactivation, induces the production of inflammatory mediators. Moreover, calcineurin is also involved in the alterations of the podocyte phenotype, which contribute to proteinuria and kidney damage observed in LN patients. Therefore, calcineurin inhibitors have been postulated as a potential treatment strategy in LN, since they reduce T cell activation and promote podocyte cytoskeleton stabilization, both being key aspects in the development of LN. Here, we review the role of calcineurin in SLE and the latest findings about calcineurin inhibitors and their mechanisms of action in the treatment of LN.

Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases.

Systemic rheumatic diseases are a heterogeneous group of autoimmune disorders that affect the connective tissue, characterized by the involvement of multiple organs, leading to disability, organ failure and premature mortality. Despite the advances in recent years, the therapeutic options for these diseases are still limited and some patients do not respond to the current treatments. Interleukin-17 (IL-17) is a cytokine essential in the defense against extracellular bacteria and fungi. Disruption of IL-17 homeostasis has been associated with the development and progression of rheumatic diseases, and the approval of different biological therapies targeting IL-17 for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has highlighted the key role of this cytokine. IL-17 has been also implicated in the pathogenesis of systemic rheumatic diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) and systemic sclerosis (SSc). The aim of this review is to summarize and discuss the most recent findings about the pathogenic role of IL-17 in systemic rheumatic and its potential use as a therapeutic option.