Identification of galectin-3 as an autoantigen in patients with IgG4-related disease

Perugino, Cory A.; AlSalem, Sultan B.; Mattoo, Hamid; Della-Torre, Emanuel; Mahajan, Vinay S.; Ganesh, Gayathri; Allard-Chamard, Hugues; Wallace, Zachary S; Montesi, Sydney B.; Kreuzer, Johannes; Haas, Wilhelm; Stone, John H.; Pillai, Shiv

doi:10.1016/j.jaci.2018.05.011

Cited by 141 publications

(106 citation statements)

References 36 publications

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“…On the other hand, US scientists have identified galectin-3, a b-galactoside-binding lectin, as an autoantigen for IgG4-RD by immunoaffinity chromatography and mass spectrometry using plasma blast clones from IgG4-RD [29]. Some 28% of 121 patients with IgG4-RD were positive for anti-galectin-3 antibody.…”

Section: Do Autoantibodies To Self-antigens Cause Immunoglobin G4-relmentioning

confidence: 99%

The front line of research into immunoglobin G4-related disease - Do autoantibodies cause immunoglobin G4-related disease?

Umehara

Okazaki

Kawano

et al. 2019

Modern Rheumatology

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IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. Although IgG4-RD is attracting strong attention as a new clinical entity, the pathogenesis of IgG4-RD and the roles of IgG4 are still unknown. Recently, self-antigens including Laminin 511 E8, Galectin-3 and Annexin A11, have been reported from one to the next as autoantigens which may be involved in the pathogenesis of IgG4-RD. In this review, we describe up-to-date information on the research of this emerging disease entity. Moreover, we discuss the pathogenesis of IgG4-RD by focusing on recent reports concerning autoantibodies. ARTICLE HISTORY

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Section: Do Autoantibodies To Self-antigens Cause Immunoglobin G4-relmentioning

confidence: 99%

The front line of research into immunoglobin G4-related disease - Do autoantibodies cause immunoglobin G4-related disease?

Umehara

Okazaki

Kawano

et al. 2019

Modern Rheumatology

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“…These observations suggest an important aspect of the pathogenesis of IgG4-RD, namely that the hyperproduction of IgG4 is frequently associated with allergy (32), suggesting a characteristic of allergic disease. Recently, both IgG4-and IgE-iso-type antibodies against galectin-3 produced by plasmablasts clones have been reported in patients with IgG4-RD (33). Although further investigation is required, the mechanism underlying isotype switching of immunoglobins to IgG4/IgE may be important in the pathogenesis of IgG4-RD (19).…”

Section: Igg4-related Hypophysitismentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Autoimmune hypopituitarism: novel mechanistic insights

Takahashi¹

2020

European Journal of Endocrinology

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Hypopituitarism is caused by various insults to the pituitary, such as hypothalamic and pituitary tumors, inflammation, autoimmunity, vascular injury, genetic abnormalities, irradiation, and trauma. Recently, it has been found that autoimmunity to the pituitary involves many pathological conditions associated with specific or non-specific hormone deficiencies in the gland. This review discusses the recent findings on the underlying mechanism of autoimmune hypopituitarism particularly of lymphocytic hypophysitis, IgG4-related hypophysitis, immune checkpoint inhibitor-induced hypophysitis, anti-PIT-1 hypophysitis, and isolated ACTH deficiency.

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“…Reactivity against multiple autoantigens in a subset of IgG4-RD patients. We previously reported that 28% of subjects from a cohort of 121 IgG4-RD patients had autoantibodies directed against galectin-3 (7). We examined the reactivity in patients in the present cohort who had data available regarding galectin-3 antibody responses (n = 86).…”

Section: Frequencies Of Annexin A11 and Laminin 511-e8mentioning

confidence: 99%

“…Since 2015, 4 autoantigens have been described as potential triggers for IgG4‐RD: prohibitin, annexin A11, laminin 511‐E8, and galectin‐3 . However, validation of these findings using external patient cohorts and characterization of the relationship between these specific autoantigens has yet to be achieved.…”

Section: Introductionmentioning

confidence: 99%

“…These observations support the possibility that IgG4-RD is an autoimmune disease, with an important role for adaptive immune responses in the associated tissue fibrosis. Since 2015, 4 autoantigens have been described as potential triggers for IgG4-RD: prohibitin, annexin A11, laminin 511-E8, and galectin-3 (5)(6)(7)(8). However, validation of these findings using external patient cohorts and characterization of the relationship between these specific autoantigens has yet to be achieved.…”

Section: Introductionmentioning

confidence: 99%

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Disease Severity Linked to Increase in Autoantibody Diversity in IgG4‐Related Disease

Liu

Perugino

Ghebremichael

et al. 2020

Arthritis & Rheumatology

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Objective Four autoantigens have been described recently in IgG4‐related disease (IgG4‐RD): prohibitin, annexin A11, laminin 511‐E8, and galectin‐3. However, no external validation has been performed, and the possibility that some individuals break tolerance to more than 1 autoantigen has not been explored. We undertook this study to evaluate the relative frequencies of antibody responses against these autoantigens in order to explore the role of adaptive immune response in IgG4‐RD. Methods Autoantibody responses against prohibitin, annexin A11, and laminin 511‐E8 were measured among a clinically diverse cohort of IgG4‐RD patients (n = 100) using enzyme‐linked immunosorbent assays. Autoantibody responses were correlated with disease severity and organ distribution. Results The frequencies of IgG4 autoantibody responses against prohibitin (10%), annexin A11 (12%), and laminin 511‐E8 (7%) were not significantly different from those of controls. A portion of the cohort (n = 86) had been analyzed previously at our center for anti–galectin‐3 antibody responses, with 25 patients (29%) having IgG4 anti–galectin‐3 antibodies. Of these 86 patients, 32 (37%) had IgG4 antibodies to ≥1 of the 4 autoantigens and 12 (14%) showed reactivity with ≥2 of the tested antigens. The subset of patients with ≥2 autoantibodies had higher total levels of IgG1, IgG2, IgG4, and C‐reactive protein, were more commonly hypocomplementemic, and were more likely to have visceral organ involvement. Conclusion Antibodies against prohibitin, annexin A11, and laminin 511‐E8 were found in only a small portion of patients with IgG4‐RD. A subset of IgG4‐RD patients, however, had IgG4 antibodies against ≥2 autoantigens. These patients presented with robust IgG subclass elevations, complement consumption, and visceral organ involvement. This broader break in immunologic tolerance in IgG4‐RD was associated with more severe disease.

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Identification of galectin-3 as an autoantigen in patients with IgG4-related disease

Cited by 141 publications

References 36 publications

The front line of research into immunoglobin G4-related disease - Do autoantibodies cause immunoglobin G4-related disease?

The front line of research into immunoglobin G4-related disease - Do autoantibodies cause immunoglobin G4-related disease?

MECHANISMS IN ENDOCRINOLOGY: Autoimmune hypopituitarism: novel mechanistic insights

Disease Severity Linked to Increase in Autoantibody Diversity in IgG4‐Related Disease

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