Identification of antibodies against extracellular matrix proteins in human osteoarthritis

Ruthard, Johannes; Hermes, Gabriele; Hartmann, Ursula; Sengle, Gerhard; Pongratz, Georg; Ostendorf, Benedikt; Schneider, Matthias; Höllriegl, Stefan; Zaucke, Frank; Wagener, Raimund; Streichert, Thomas; Klatt, Andreas R.

doi:10.1016/j.bbrc.2018.07.036

Cited by 15 publications

(12 citation statements)

References 24 publications

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“…Although there is a paucity of studies examining the role of anti-ECM antibodies in autoimmunity, the work published to date suggests these may play an important role in disease. In a study comparing sera derived from patients with rheumatoid arthritis (RA) to that from healthy donors, IgG autoantibodies directed against the ECM components thrombospondin-4, cartilage oligomeric matrix protein, and collagen type II were identified more frequently in RA patients when compared to healthy controls (35). Corroborative work examined anti-ECM antibodies in the synovial fluid of RA patients and those with osteoarthritis (OA) and found that anti-Bgn IgM and IgG antibodies were elevated in the synovium of RA patients when compared to those with OA (36).…”

Section: Anti-ecm Antibodies May Contribute To Tissue Destruction Directly In Autoimmunitymentioning

confidence: 99%

Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren’s Syndrome

et al. 2021

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Primary Sjögren’s syndrome is an autoimmune disease that is predominantly seen in women. The disease is characterized by exocrine gland dysfunction in combination with serious systemic manifestations. At present, the causes of pSS are poorly understood. Pulmonary and renal inflammation are observed in pSS mice, reminiscent of a subset of pSS patients. A growing body of evidence indicates that inflammation mediated by Damage-Associated Molecular Patterns (DAMPs) contributes to autoimmunity, although this is not well-studied in pSS. Degraded extracellular matrix (ECM) constituents can serve as DAMPs by binding pattern-recognition receptors and activating Myd88-dependent signaling cascades, thereby exacerbating and perpetuating inflammatory cascades. The ECM components biglycan (Bgn) and decorin (Dcn) mediate sterile inflammation and both are implicated in autoimmunity. The objective of this study was to determine whether these ECM components and anti-ECM antibodies are altered in a pSS mouse model, and whether this is dependent on Myd88 activation in immune cells. Circulating levels of Bgn and Dcn were similar among pSS mice and controls and tissue expression studies revealed pSS mice had robust expression of both Bgn and Dcn in the salivary tissue, saliva, lung and kidney. Sera from pSS mice displayed increased levels of autoantibodies directed against ECM components when compared to healthy controls. Further studies using sera derived from conditional knockout pSS mice demonstrated that generation of these autoantibodies relies, at least in part, on Myd88 expression in the hematopoietic compartment. Thus, this study demonstrates that ECM degradation may represent a novel source of chronic B cell activation in the context of pSS.

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Section: Anti-ecm Antibodies May Contribute To Tissue Destruction Directly In Autoimmunitymentioning

confidence: 99%

Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren’s Syndrome

et al. 2021

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“…Although OA is not considered an autoimmune disorder, the immune system is highly related with early disease 24. However, existing literature related to the presence of AAbs in patients with OA is limited 8 25–27. Indeed, this is the first study that evaluates the usefulness of AAbs to stratify patients with asymptomatic OA.…”

Section: Discussionmentioning

confidence: 98%

Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative

et al. 2019

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ObjectiveTo find autoantibodies (AAbs) in serum that could be useful to predict incidence of radiographic knee osteoarthritis (KOA).DesignA Nucleic-acid Programmable Protein Arrays (NAPPA) platform was used to screen AAbs against 2125 human proteins in sera at baseline from participants free of radiographic KOA belonging to the incidence and non-exposed subcohorts of the Osteoarthritis Initiative (OAI) who developed or not, radiographic KOA during a follow-up period of 96 months. NAPPA-ELISA were performed to analyse reactivity against methionine adenosyltransferase two beta (MAT2β) and verify the results in 327 participants from the same subcohorts. The association of MAT2β-AAb levels with KOA incidence was assessed by combining several robust biostatistics analysis (logistic regression, Receiver Operating Characteristic and Kaplan-Meier curves). The proposed prognostic model was replicated in samples from the progression subcohort of the OAI.ResultsIn the screening phase, six AAbs were found significantly different at baseline in samples from incident compared with non-incident participants. In the verification phase, high levels of MAT2β-AAb were significantly associated with the future incidence of KOA and with an earlier development of the disease. The incorporation of this AAb in a clinical model for the prognosis of incident radiographic KOA significantly improved the identification/classification of patients who will develop the disorder. The usefulness of the model to predict radiographic KOA was confirmed on a different OAI subcohort.ConclusionsThe measurement of AAbs against MAT2β in serum might be highly useful to improve the prediction of OA development, and also to estimate the time to incidence.

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“…Interestingly, the fact that cartilage ECM components and cleavage products might stimulate the immune system or even exert biological functions in the joint has only been recognized in recent years. Indeed, several studies have shown that antibodies directed against cartilage matrix proteins or fragments can be detected in serum samples of patients suffering from OA [ 76 ] and RA [ 77 ]. In a recent elegant study, a functional coupling between such autoantibodies and pain has been demonstrated.…”

Section: The Role Of Proteases and Cytokines In Oamentioning

confidence: 99%

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

Grässel

Zaucke

Madry

2021

JCM

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Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% of the world’s population over 60 years of age suffers from symptomatic (painful, disabling) OA. The disease poses a tremendous economic burden on the health-care system and society for diagnosis, treatment, sick leave, rehabilitation, and early retirement. Most patients also experience sleep disturbances, reduced capability for exercising, lifting, and walking and are less capable of working, and maintaining an independent lifestyle. For patients, the major problem is disability, resulting from joint tissue destruction and pain. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Here, we elucidate novel concepts and hypotheses regarding disease progression and pathology, which are relevant for understanding underlying the molecular mechanisms as a prerequisite for future therapeutic approaches. Emphasis is placed on topographical modeling of the disease, the role of proteases and cytokines in OA, and the impact of the peripheral nervous system and its neuropeptides.

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Identification of antibodies against extracellular matrix proteins in human osteoarthritis

Cited by 15 publications

References 24 publications

Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren’s Syndrome

Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren’s Syndrome

Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

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