Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens.

Introduction: We have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA).

Methods: The autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC® system.

Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis.

Objective: The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen-derived peptides for reactivity before the onset of RA symptoms.

Methods: A case-control study was conducted within the Medical Biobank of Northern Sweden.

Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides.

Introduction: Autoantibodies directed against citrullinated proteins/peptides (ACPAs) are highly specific and predictive for the development of rheumatoid arthritis (RA). Different subgroups of RA patients, which have different prognoses and may require different treatments, are characterized by different autoantibody profiles. The objective of this study was to develop a microarray for the detection of multiple RA-associated autoantibodies, initially focusing on responses against citrullinated epitopes on candidate autoantigens in RA.

Antibodies to citrullinated α-enolase peptide 1 and clinical and radiological outcomes in rheumatoid arthritis.

Introduction: The anticyclic citrullinated peptide 2 (anti-CCP2) assay is a generic test for antibodies to citrullinated proteins, among which there is a subset of about 50% with antibodies to citrullinated enolase peptide 1 (CEP-1). The anti-CEP-1 positive subset is strongly associated with the HLA-DRB1 shared epitope and its interaction with smoking.

Objective: To investigate whether anti-CEP-1 antibodies may be helpful in predicting outcome.

The inhibitory Fc gamma IIb receptor dampens TLR4-mediated immune responses and is selectively up-regulated on dendritic cells from rheumatoid arthritis patients with quiescent disease.

Rheumatoid arthritis (RA) is a common autoimmune disease leading to profound disability and premature death. Although a role for FcgammaRs and TLRs is accepted, their precise involvement remains to be elucidated. FcgammaRIIb is an inhibitory FcR important in the maintenance of tolerance.

Regulation of the interferon-alpha production induced by RNA-containing immune complexes in plasmacytoid dendritic cells.

Objective: Interferon-alpha (IFNalpha) is produced in several autoimmune diseases, including systemic lupus erythematosus (SLE), and may be important in their pathogenesis. We undertook this study to investigate how IFNalpha production induced by RNA-containing immune complexes (ICs) in plasmacytoid dendritic cells (PDCs) is regulated.

Methods: Normal PDCs purified from peripheral blood mononuclear cells (PBMCs) were cocultivated with other cell populations isolated from healthy individuals or SLE patients.

Immune complex-mediated cytokine production is regulated by classical complement activation both in vivo and in vitro.

Immune complexes (IC) induce a number of cellular functions, including the enhancement of cytokine production from monocytes, macrophages and plasmacytoid dendritic cells. The range and the composition of cytokines induced by IC in vitro is influenced by the availability of an intact classical complement cascade during cell culture, as we have showed in our studies on artificial IC and on cryoglobulins purified from patients with lymphoproliferative diseases. When IC purified from systemic lupus erythematosus sera were used to stimulate in vitro cytokine production, the amount of circulating IC and IC-induced cytokine levels depended both on in vivo classical complement function as well as on the occurrence of anti-SSA, but not on anti-dsDNA or any other autoantibodies.

Profound and paradoxical impact on arthritis and autoimmunity of the rat antigen-presenting lectin-like receptor complex.

Objective: The antigen-presenting lectin-like receptor complex (APLEC) was recently identified as a genetic determinant for arthritis susceptibility. We undertook this study to define mechanisms underlying the impact of APLEC on arthritis, to determine whether sex effects occur, and to determine whether APLEC influences different types of arthritis and phenotypes other than susceptibility.

Methods: Arthritis-susceptible DA rats were compared with sex-matched congenic rats in which APLEC alleles were substituted with alleles from arthritis-resistant PVG rats.

Antibodies against citrullinated vimentin in rheumatoid arthritis: higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides.

Objective: The Sa autoantigen can be found in inflamed synovium of patients with rheumatoid arthritis (RA), and at least part of the humoral RA-specific anti-Sa response is directed against citrullinated vimentin. This study was undertaken to evaluate the sensitivity, specificity, and prognostic value of determination of levels of antibodies against modified citrullinated vimentin (anti-MCV) as compared with antibodies against cyclic citrullinated peptides (anti-CCP) in an inception cohort of patients with early RA.

Methods: Clinical data, radiographs, and measurements of levels of anti-MCV and anti-CCP antibodies were obtained in 273 patients with early RA at baseline, after 3 months, and after 1, 2, 3, and 5 years.

Circulating immune complexes (IC) and IC-induced levels of GM-CSF are increased in sudanese patients with acute visceral Leishmania donovani infection undergoing sodium stibogluconate treatment: implications for disease pathogenesis.

Infection with Leishmania donovani is associated with IL-10 as well as with GM-CSF. Immune complexes (IC) exert important functions by stimulation of monocytes/macrophage-mediated production of pro- and anti-inflammatory cytokines in rheumatic diseases. In this investigation, we have explored IC-induced cytokine production during Leishmania infection.

Inflammatory cytokines, behaviour and age as determinants of self-rated health in women.

Self-rated health is a powerful and independent predictor of long-term health, but its biological basis is unknown. We have shown previously that self-rated health is associated with increased levels of circulating cytokines in women. The main aim of the present study was to increase the understanding of the association between markers of wellbeing, such as self-rated health, and cytokines and to investigate the impact of age on these associations.

High anti-collagen type-II antibody levels and induction of proinflammatory cytokines by anti-collagen antibody-containing immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset.

Objective: To investigate whether the cytokine-inducing properties of surface-bound collagen type II (CII)-containing immune complexes (IC), which were reported earlier, have any clinical impact.

Methods: Anti-CII serology was analysed in 274 patients with early rheumatoid arthritis (RA). Patients with increased levels of anti-CII were followed serially for 1-5 years with regard to anti-CII IC-induced levels of tumour necrosis factor (TNF)alpha, interleukin (IL)1beta and IL8.

Surface-bound anti-type II collagen-containing immune complexes induce production of tumor necrosis factor alpha, interleukin-1beta, and interleukin-8 from peripheral blood monocytes via Fc gamma receptor IIA: a potential pathophysiologic mechanism for humoral anti-type II collagen immunity in arthritis.

Objective: Type II collagen (CII) is a major component of hyaline cartilage, and antibodies against CII are found in a subgroup of patients with rheumatoid arthritis. We undertook this study to investigate whether and how antibodies directed against CII can form solid-phase immune complexes (ICs) with cytokine-inducing properties in a model theoretically resembling the situation in the inflamed joint, in which CII is exposed for interaction with anti-CII antibodies during periods of inflammation.

Methods: Sixty-five arthritis patients with varying levels of anti-native CII antibodies and 10 healthy controls were evaluated concerning anti-CII and cytokines induced in a solid-phase IC model.

Immune complexes from rheumatoid arthritis synovial fluid induce FcgammaRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-alpha by peripheral blood mononuclear cells.

Immune complexes (ICs) can induce production of cytokines by peripheral blood mononuclear cells via Fc receptors. Rheumatoid factor (RF) develop in response to ICs in many clinical and experimental settings. We investigated whether and how polyethylene glycol (PEG) precipitated ICs from rheumatoid arthritis (RA) sera and synovial fluid (SF) can influence cytokine production by peripheral blood mononuclear cells.

Cryoglobulin-induced cytokine production via FcgammaRIIa: inverse effects of complement blockade on the production of TNF-alpha and IL-10. Implications for the growth of malignant B-cell clones.

Monoclonal antibodies produced by patients with lymphoproliferative diseases sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly agglutinate and form immune complexes (IC) when cooled below normal body temperature or through variation in pH and ionic strength. In accordance with our findings of IC-induced cytokine production from peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also induce cytokine production. One IgG and one IgM type I CG from two patients with multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified and added to PBMC cultures.