From Insect Bites to a Skin Autoimmune Disease: A Conceivable Pathway to Endemic Pemphigus Foliaceus

Li, Ning; Aoki, Valéria; Li, Zhi; Prisayanh, Phillip; Valenzuela, Jesús G.; Díaz, Luis A.

doi:10.3389/fimmu.2022.907424

Cited by 7 publications

(9 citation statements)

References 82 publications

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“…4a ). In these patients, antibodies develop against a salivary antigen from flies that are cross-reactive with desmogleins 93 , 94 . Moreover, monoclonal antibodies derived from patients with pemphigus vulgaris were shown to be cross-reactive with walnut antigen 95 .…”

Section: Igg4-dependent Pathologymentioning

confidence: 99%

The unique properties of IgG4 and its roles in health and disease

Rispens

Huijbers

2023

Nat Rev Immunol

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IgG4 is the least abundant subclass of IgG in human serum and has unique functional features. IgG4 is largely unable to activate antibody-dependent immune effector responses and, furthermore, undergoes Fab (fragment antigen binding)-arm exchange, rendering it bispecific for antigen binding and functionally monovalent. These properties of IgG4 have a blocking effect, either on the immune response or on the target protein of IgG4. In this Review, we discuss the unique structural characteristics of IgG4 and how these contribute to its roles in health and disease. We highlight how, depending on the setting, IgG4 responses can be beneficial (for example, in responses to allergens or parasites) or detrimental (for example, in autoimmune diseases, in antitumour responses and in anti-biologic responses). The development of novel models for studying IgG4 (patho)physiology and understanding how IgG4 responses are regulated could offer insights into novel treatment strategies for these IgG4-associated disease settings.

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Section: Igg4-dependent Pathologymentioning

confidence: 99%

The unique properties of IgG4 and its roles in health and disease

Rispens

Huijbers

2023

Nat Rev Immunol

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“…Certain antigens are known to drive IgG4 responses, such as bee venom and certain biologicals [99]. Specifically for pemphigus there is evidence of desmoglein 1/3 autoantibody development following exposure to walnut or sand fly antigens [41][42][43]. There is no evidence yet for comparable molecular mimicry events in other IgG4-AID.…”

Section: Discussionmentioning

confidence: 99%

“…Class switching to IgG4 is known to occur in response to prolonged exposure to certain antigens such as bee venom and peanuts [5,36] or under influence of Th2 cytokines IL-4, IL-10 and IL-13 [37][38][39][40]. Indeed, these cytokines were found increased in IgG4-AID patients and cross-reactivity was observed with autoantibodies from pemphigus patients with IgG4-inducing allergens [41][42][43]. Lastly, dysregulated B cell maturation or aberrant class switching may cause overrepresentation of IgG4 + B cells and IgG4 plasma cells in immune responses.…”

Section: Introductionmentioning

confidence: 99%

Autoantibody subclass predominance is not driven by aberrant class switching or impaired B cell development

Paardekooper

Fillié-Grijpma

Sluijs-Gelling

et al. 2023

Preprint

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A subset of autoimmune diseases is characterized by predominant pathogenic IgG4 autoantibodies (IgG4-AIDs). Why IgG4 predominates in these disorders is unknown. We hypothesized that dysregulated B cell maturation or aberrant class switching causes overrepresentation of IgG4+ B cells and plasma cells. Therefore, we compared the B cell compartment of patients with muscle-specific kinase (MuSK) myasthenia gravis (MG), pemphigus, leucine-rich glioma inactivated (LGI1) encephalitis and contactin-associated protein-like 2 (CASPR2) encephalitis (four IgG4-AIDs) to patients with acetylcholine receptor (AChR) MG, Lambert-Eaton myasthenic syndrome (LEMS) (two IgG1-3-AIDs) and age-matched healthy donors, using flow cytometry. B cell subset relative abundance at all maturation stages was normal, except for a, possibly treatment-related, reduction in immature and naive CD5+ cells in IgG4-AIDs. IgG4+ B cell and plasma cell fractions were normal in IgG4-AID patients, however they had an (sub)class-independent 8-fold increase in circulating mature CD20-CD138+ plasma cells. No autoreactivity was found in this subset after sorting. In conclusion, patients with IgG4-AID do not show increased numbers of IgG4-expressing cells. These results argue against aberrant B cell development in these patients and rather suggest the autoantibody subclass predominance to be antigen-driven. The similarities between B cell subset numbers among these patients suggest that these IgG4-AIDs, despite displaying variable clinical phenotypes, share a similar underlying immune profile.

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“…For example, if antigens of pathogenic microorganisms such as bacteria and viruses are in a molecular mimicry relationship with self-antigens, immune responses to infections may cause autoimmune diseases. 2,3 Autoimmune diseases caused by molecular mimicry could also be caused by vaccines. However, cases of PV occurring after vaccination are rare.…”

Section: Pemphigus Vulgaris With Advanced Hypopharyngeal and Gastric ...mentioning

confidence: 99%

“…5 In the same way, vaccines against COVID19 have been described to cause autoimmune abnormalities as an adverse effect. 2,3 These indicate that there is a molecular mimicry between COVID19 antigens and self-antigens, possibly triggering autoimmune abnormalities in the immune response to COVID19.…”

Section: E75mentioning

confidence: 99%