B cell apotopes of the 60-kDa Ro/SSA and La/SSB autoantigens

Reed, Joanne H.; Jackson, Michael; Gordon, Thomas P.

doi:10.1016/j.jaut.2008.04.008

Cited by 34 publications

(20 citation statements)

References 40 publications

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“…However, as Michelle Petri says about SLE [28], the diagnosis of systemic autoimmune diseases should take into account less specific features (such as arthritis, cytopenia, Raynaud phenomenon, or neurological involvement, among others) that could act as "clues" to identify incident SS cases. Patients with anti-Ro and positive salivary biopsy probably form a homogeneous subset of patients with a specific etiopathogenic mechanism (lymphocytic infiltration of the exocrine glands, B-cell hyperactivity, and local production of Ro/La antigens, [29][30][31][32][33][34][35]) who present with a more pronounced systemic and autoimmune expression. In contrast, etiopathogenic mechanisms other than lymphocytic-mediated epithelial damage [4] could be involved in patients with negative Ro and negative biopsy, who predominantly present with a sicca-limited involvement.…”

Section: Discussionmentioning

confidence: 99%

Sjögren Syndrome or Sjögren Disease? The Histological and Immunological Bias Caused by the 2002 Criteria

Ramos-Casals¹,

Brito-Zerón²,

Pérez-de-Lis

et al. 2009

Clinic Rev Allerg Immunol

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The current 2002 classification criteria do not cover the broad clinical and immunological heterogeneity of primary Sjögren syndrome (SS), since five of the six criteria focus exclusively on glandular involvement and the remaining criterion is the mandatory presence of anti-Ro/La antibodies. The aim of this study was to analyze the clinical features of patients with a well-established diagnosis of primary SS who do not fulfill the 2002 classification criteria. Five hundred seven patients diagnosed with primary SS (1993 criteria) were consecutively included and followed up. Two hundred twenty-one (44%) patients did not fulfill the 2002 criteria. These patients were older at diagnosis (p < 0.001) and had a lower frequency of parotid enlargement (p = 0.002), fever (p = 0.041), arthritis (p = 0.041), vasculitis (p = 0.050), peripheral neuropathy (p = 0.002), cranial nerve involvement (p = 0.015), raised erythrocyte sedimentation rate ( ESR) levels (p < 0.001), anemia (p < 0.001), leukopenia (p = 0.037), hypergammaglobulinemia (p < 0.001), positive rheumatoid factor ( RF; p = 0.002), and cryoglobulinemia (p = 0.049) in comparison with those fulfilling 2002 criteria. However, there were no significant differences in the prevalence of sicca features, diagnostic tests, overall systemic involvement, antinuclear antibodies , complement levels, development of B-cell lymphoma, or survival. Patients with anti-Ro antibodies had the highest frequencies of systemic features, hematological abnormalities, and altered immunological markers. In conclusion, patients fulfilling the 2002 criteria, who have either a specific histological diagnosis (lymphocytic infiltration) or highly specific autoantibodies (Ro/La), might well be considered to have Sjögren "disease." In contrast, etiopathogenic mechanisms other than lymphocytic-mediated epithelial damage could be involved in patients with negative Ro and negative biopsy, in whom the term Sjögren "syndrome" seems more adequate.

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Section: Discussionmentioning

confidence: 99%

Sjögren Syndrome or Sjögren Disease? The Histological and Immunological Bias Caused by the 2002 Criteria

Ramos-Casals¹,

Brito-Zerón²,

Pérez-de-Lis

et al. 2009

Clinic Rev Allerg Immunol

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“…An apotope, defined as an epitope expressed on the surface of early or late apoptotic cells following translocation of intracellular autoantigen, can be bound by a specific autoantibody, leading to the formation of pathogenic IgG-apoptotic cell immune complexes or impaired clearance of apoptotic cells by neighboring cells [51]. The efficient phagocytosis of apoptotic cells by macrophages is an important regulatory process during inflammation.…”

Section: Autoimmunity and The Clearance Of Apoptotic Cellsmentioning

confidence: 99%

Primary biliary cirrhosis and autoimmune hepatitis: apotopes and epitopes

et al. 2010

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Autoimmune liver diseases (ALDs) represent a wide spectrum of chronic inflammatory diseases that are characterized by an immune-mediated attack against either hepatocytes (in the case of autoimmune hepatitis types 1 and 2, AIH-1, 2) or cholangiocytes (in primary biliary cirrhosis, PBC). PBC is considered a model autoimmune disease due to the homogeneity of patients, the high specificity of antimitochondrial antibodies (AMAs), and the specificity of biliary epithelial cell (BEC) destruction. It ensues from a multi-lineage loss of tolerance to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). One of the major unanswered questions in the pathogenesis of PBC is the specificity of small intrahepatic bile duct attack while PDC-E2 is present in mitochondria of nucleated cells. Recent findings suggest that the apoptosis of BECs may be of considerable importance for understanding PBC, and that they are more than simply an innocent victim of an immune attack. Rather, they attract immune attack by virtue of the unique biochemical mechanisms by which they handle PDC-E2. The role of apoptotic cells in AIH is not well defined, but advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen (CYP2D6) is known, enabling the characterization of antigen-specific immune responses. This review article is intended to provide a critical overview of current evidence on tissue specificity in ALDs, as well as the characteristics of the relevant epitopes and apotopes and their biological and clinical significance.

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“…Recent advances have been made in immuno-patho-physiology of this cytokine [18], so that we are likely to learn more about autoimmune diseases. For additional readings on the role of B cells and potential interactions with either IL-6 or related cytokines, we refer to several recent publications [51][52][53][54][55][56][57]. Finally, we should emphasize with the emergence of the biologics the potential consequences of toxicity [58].…”

Section: Perspectives In Biotherapymentioning

confidence: 99%