Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjogren's syndrome and systemic lupus erythematosus

Pourmand, Nader; Wahren‐Herlenius, Marie; Gunnarsson, Iva; Svenungsson, Elisabet; Löfström, Björn; Ioannou, Y; Isenberg, David; Magnusson, Carl

doi:10.1136/ard.58.10.623

Cited by 30 publications

(20 citation statements)

References 47 publications

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“…Early studies (33) suggested a correlation between deposition of IgA and/or IgM immune complexes and clinical manifestations of SjS; however, Cuida et al (37) reported the presence in both saliva and salivary glands of SjS patients of complement regulatory proteins, including protectin (CD59), decay accelerating factor (CD55), membrane cofactor protein (CD46), and clusterin (SP-40; Ref. 38), that prevented complement activation on the tissues.…”

Section: Discussionmentioning

confidence: 99%

“…With the appearance of T and B lymphocytes within the submandibular glands of C57BL/6.NOD-Aec1Aec2 mice, plus the detectable changes within their splenic B cell populations, an increasing number of serum autoantibodies can be detected (33)(34)(35)(36). Of particular importance in human SjS disease (but not in SjS-like disease of NOD mice) are the ANAs, especially anti-SS-A/Ro and anti-SS-B/La, as the presence of these ANAs in the sera of human SjS patients is one of the diagnostic markers for clinical disease (4).…”

Section: Aec1aec2c3mentioning

confidence: 99%

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Development of Sjögren’s Syndrome in Nonobese Diabetic-Derived Autoimmune-Prone C57BL/6.NOD-Aec1Aec2 Mice Is Dependent on Complement Component-3

Nguyen

Kim

Cornelius

et al. 2007

The Journal of Immunology

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The role of complement in the etiology of Sjögren’s syndrome (SjS), a human autoimmune disease manifested primarily by salivary and lacrimal gland dysfunction resulting in dry mouth/dry eye syndrome, remains ill-defined. In the present study, we examined the role of complement component-3 (C3) using a newly constructed C3-gene knockout mouse, C57BL/6.NOD-Aec1Aec2.C3−/−. Inactivation of C3 in the parental C57BL/6.NOD-Aec1Aec2 strain, a model of primary SjS, resulted in a diminished or total absence of both preclinical and clinical manifestations during development and onset of disease, including reduced acinar cell apoptosis, reduced levels of caspase-3, lack of leukocyte infiltration of submandibular glands, reduced synthesis of disease-associated autoantibodies, maintenance of normal glandular architecture, and retention of normal saliva secretion. In addition, C57BL/6-NOD.Aec1Aec2.C3−/− mice did not exhibit increased numbers of marginal zone B cells, a feature of SjS-prone C57BL/6-NOD.Aec1Aec2 mice. Interestingly, C57BL/6-NOD.Aec1Aec2.C3−/− mice retained some early pathological manifestations, including activation of serine kinases with proteolytic activity for parotid secretory protein. This improvement in the clinical manifestations of SjS-like disease in C57BL/6.NOD-Aec1Aec2.C3−/− mice, apparently a direct consequence of C3 deficiency, supports a much more important role for complement in the adaptive autoimmune response than previously recognized, possibly implicating an essential role for innate immunity.

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Section: Discussionmentioning

confidence: 99%

Section: Aec1aec2c3mentioning

confidence: 99%

Development of Sjögren’s Syndrome in Nonobese Diabetic-Derived Autoimmune-Prone C57BL/6.NOD-Aec1Aec2 Mice Is Dependent on Complement Component-3

Nguyen

Kim

Cornelius

et al. 2007

The Journal of Immunology

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“…In SjS patients, numerous autoantibodies have been identified, the more important ones being Abs reactive with intracellular ribonuclear proteins, in particular Ro/SS-A and La/SS-B (27). Autoantibodies to these nuclear proteins can be of either IgM, IgG, or IgA (29), with titers of IgA isotype-specific autoantibodies to Ro/SS-A and La/SS-B Ags correlating with sicca syndrome in primary SjS (29). In addition, levels of anti-Ro/SS-A and anti-La/SS-B have been reported to show a strong association with the titers of rheumatoid factor prevalent in patients with primary SjS (11), and while the levels of rheumatoid factor were not directly related to the disease state, they were highly significant in those patients developing extraglandular manifestations (11).…”

Section: Discussionmentioning

confidence: 99%

IL-4-STAT6 Signal Transduction-Dependent Induction of the Clinical Phase of Sjögren’s Syndrome-Like Disease of the Nonobese Diabetic Mouse

Nguyen

Gao

Kim

et al. 2007

The Journal of Immunology

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NOD.B10-H2b and NOD/LtJ mice manifest, respectively, many features of primary and secondary Sjögren’s syndrome (SjS), an autoimmune disease affecting primarily the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes). B lymphocytes play a central role in the onset of SjS with clinical manifestations dependent on the appearance of autoantibodies reactive to multiple components of acinar cells. Previous studies with NOD.IL4−/− and NOD.B10-H2b.IL4−/− mice suggest that the Th2 cytokine, IL-4, plays a vital role in the development and onset of SjS-like disease in the NOD mouse model. To investigate the molecular mechanisms by which IL-4 controls SjS development, a Stat6 gene knockout mouse, NOD.B10-H2b.C-Stat6−/−, was constructed and its disease profile was defined and compared with that of NOD.B10-H2b.C-Stat6+/+ mice. As the NOD.B10-H2b.C-Stat6−/− mice aged from 4 to 24 wk, they exhibited leukocyte infiltration of the exocrine glands, produced anti-nuclear autoantibodies, and showed loss and gain of saliva-associated proteolytic enzymes, similar to NOD.B10-H2b.C-Stat6+/+ mice. In contrast, NOD.B10-H2b.C-Stat6−/− mice failed to develop glandular dysfunction, maintaining normal saliva flow rates. NOD.B10-H2b.C-Stat6−/− mice were found to lack IgG1 isotype-specific anti-muscarinic acetylcholine type-3 receptor autoantibodies. Furthermore, the IgG fractions from NOD.B10-H2b.C-Stat6−/− sera were unable to induce glandular dysfunction when injected into naive recipient C57BL/6 mice. NOD.B10-H2b.C-Stat6−/− mice, like NOD.B10-H2b.IL4−/− mice, are unable to synthesize IgG1 Abs, an observation that correlates with an inability to develop end-stage clinical SjS-like disease. These data imply a requirement for the IL-4/STAT6-pathway for onset of the clinical phase of SjS-like disease in the NOD mouse model.

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“…Aberrant expression of select cytokines may thus underlie abnormal homing of B1a cells to the Irgm1 -/-lung as well as programming of B1a cells at that site to release IgA class natural antibodies. Suggesting human relevance, BAFF and CXCL13 are also elevated in human SS and 80% or more of primary SS patients have elevated anti-Ro and -La IgA (1,35,36).…”

Section: Discussionmentioning

confidence: 99%

Irgm1 coordinately regulates autoimmunity and host defense at select mucosal surfaces

et al. 2017

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Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjogren's syndrome and systemic lupus erythematosus

Cited by 30 publications

References 47 publications

Development of Sjögren’s Syndrome in Nonobese Diabetic-Derived Autoimmune-Prone C57BL/6.NOD-Aec1Aec2 Mice Is Dependent on Complement Component-3

Development of Sjögren’s Syndrome in Nonobese Diabetic-Derived Autoimmune-Prone C57BL/6.NOD-Aec1Aec2 Mice Is Dependent on Complement Component-3

IL-4-STAT6 Signal Transduction-Dependent Induction of the Clinical Phase of Sjögren’s Syndrome-Like Disease of the Nonobese Diabetic Mouse

Irgm1 coordinately regulates autoimmunity and host defense at select mucosal surfaces

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