Serum Detection of Anti-thyroid Peroxidase and Anti-thyroglobulin Antibodies in Chinese Patients With Pemphigus Vulgaris and Pemphigus Foliaceus and Literature Review

Wang, Hexiao; Yang, Yang; Hu, Jingyuan; Zhang, Liming; Cai, Yunfei; Guo, Hao; Xiao, Ting; Chen, Hong‐Duo; Gao, Xinghua; Qiao, Shuai

doi:10.3389/fimmu.2021.653356

Cited by 4 publications

(5 citation statements)

References 30 publications

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“…Recently, our group has shown that anti-TPO activity is heightened in the serum of North American PV patients and driven by HLA status as well as the absence of anti-Dsg3/1 reactivity (26). The presence of higher levels and rates of positivity of anti-TPO and anti-Tg antibodies in pemphigus patients compared to healthy controls was recently confirmed in the Chinese population (45). Interestingly, we found that both anti-TPO + and anti-Tg + subjects had a higher proportion of contradiction to the DCH compared to anti-TPOand anti-Tgsubjects, respectively, suggesting that these antibodies may be involved in disease pathogenesis in certain cases not explained by the DCH, such as those not exhibiting detectable levels of anti-Dsg antibodies and/or PV in underrepresented HLA haplotypes.…”

Section: B Amentioning

confidence: 83%

Desmoglein compensation hypothesis fidelity assessment in Pemphigus

et al. 2022

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The pemphigus group of autoimmune blistering diseases encompasses pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Lesion location in pemphigus has been elegantly postulated by the Desmoglein Compensation Hypothesis (DCH), which references the distribution of desmoglein (Dsg) proteins in the epidermis along with a patient’s autoantibody profile to describe three different lesion phenotypes: PF is characterized by subcorneal lesions in the presence of anti-Dsg1 antibodies only, while lesions in PV are suprabasilar and accompanied by anti-Dsg3 antibodies only in mucosal PV, or both anti-Dsg3 and anti-Dsg1 in the case of mucocutaneous PV. While the validity of this hypothesis has been supported by several studies and is prominently featured in textbooks of dermatology, a number of logical inconsistencies have been noted and exceptions have been published in several small-scale studies. We sought to comprehensively assess the extent to which patient clinical and autoantibody profiles contradict the DCH, and characterize these contradictions in a large sample size of 266 pemphigus patients. Remarkably, we find that roughly half of active PV and PF patients surveyed present with a combination of lesion morphology and anti-Dsg3/1 levels that contradict the DCH, including: patients with a cutaneous only PV presentation, mucocutaneous disease in the absence of either Dsg3, Dsg1, or both, and mucosal disease in the absence of Dsg3 or presence of Dsg1. We also find stark differences in fidelity to the DCH based on ethnicity and HLA-association, with the lowest proportion of adherence in previously understudied populations. These findings underscore the need to expand our understanding of pemphigus morphology beyond the DCH, in particular for populations that have not been a focus in previous investigation.

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Section: B Amentioning

confidence: 83%

Desmoglein compensation hypothesis fidelity assessment in Pemphigus

et al. 2022

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“…In addition to anti-Dsg3 and 1 reactivity, other autoantibodies have been described in patients with PV ( 13 – 15 ). Among these non-Dsg antibodies, anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) reactivity has been found at higher rates in PV patients than in healthy controls ( 14 , 15 ) and that we have previously described anti-TPO reactivity is driven by HLA status ( 14 ). Thus, we also assessed anti-TPO and anti-Tg reactivity in active patients divided by HLA-status ( Figure 3B ).…”

Section: Resultsmentioning

confidence: 99%

“…Overall, differences in anti-Dsg3 levels reached statistically significant levels with a p value of p=0.03363 (one-way ANOVA), while variability in anti-Dsg1 levels only approached statistical significance with p=0.05963. In addition to anti-Dsg3 and 1 reactivity, other autoantibodies have been described in patients with PV (13)(14)(15). Among these non-Dsg antibodies, anti-thyroid peroxidase (TPO) and antithyroglobulin (Tg) reactivity has been found at higher rates in PV patients than in healthy controls (14, 15) and that we have previously described anti-TPO reactivity is driven by HLA status (14).…”

Section: Autoantibody Levels Vary Significantly With Hla Statusmentioning

confidence: 85%

Patient genetics shape the autoimmune response in the blistering skin disease pemphigus vulgaris

2023

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Background and aimPemphigus vulgaris (PV) is known to have one of the strongest HLA associations among autoimmune diseases. DRB1*0402 and DQB1*0503 in particular are significantly overrepresented in PV patients in certain worldwide populations. Yet, there remain significant gaps in our understanding regarding the precise link between PV-associated HLA molecules, the specificity of the autoimmune response, and clinical expression. In this study we assessed correlations between factors including HLA genotype, ethnicity, autoantibody levels, and lesion distribution in a cohort of 293 patients.Methods and populationParticipants were recruited from multiple outpatient dermatology clinic settings and patient support meetings in the USA. On intake, patients provided venous blood samples and answered questionnaires regarding their current disease activity.ResultsEighty-one percent of patients typed as either DRB1*0402 or DQB1*0503 with a high prevalence of DRB1*0402 in patients of Ashkenazi Jewish or Caucasian (non-Jewish) descent (86% and 42%, respectively) and DQB1*0503 in patients of Southeast Asian descent (78%). Patients typing as HLA DRB1*0402 had higher levels of anti-desmoglein (Dsg)3 antibodies (204.6 +/- 340.5 IU/ml) than patients without DRB1*0402 (138.5 +/- 236.4 IU/ml) (p=0.03) and had mucosal only lesions more often than cutaneous only or mucocutaneous lesions. Patients typing as DQB1*0503 had higher levels of anti-Dsg1 antibodies (47.3 +/- 59.8 IU/ml) compared to other groups (27.8 +/- 43.7 IU/ml) (p=0.06) and higher rates of mucocutaneous disease than other lesion types. We also report an unexpected HLA association of DRB1*0804 in PV patients of African descent. Sixty-four percent of this population carried the DRB1*0804 allele, and presented with highly elevated levels of anti-Dsg3 (p=0.02). However, neither African heritage nor the presence of DRB1*0804 correlated with a predilection to any specific lesion morphology. Patients that carried neither DRB1*0402, nor DQB1*0503 or DRB1*0804 had the lowest levels of anti-Dsg3 antibodies (60.0 +/- 80.0 IU/ml) and the highest rate of solely cutaneous disease compared to carriers of these alleles.ConclusionOur data illuminate the broader impact of genetic factors on disease development by showing that differences in HLA expression among patients and ethnicities play a large role in driving distinct patterns of antibody selection and disease phenotype in PV. These findings provide insights regarding clinical heterogeneity, and are relevant to developing improved, patient tailored management strategies.

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“…17 A recent study in China found that anti-TPO and anti-TG antibody levels and antibody positivity increased in pemphigus patients compared to controls. 18 Kavala et alobserved that titers of thyroid autoimmune antibodies in the pemphigus group increased significantly. 3 Overall, the above evidence suggested that there may exist a link between pemphigus and diverse thyroid diseases.…”

Section: Discussionmentioning

confidence: 99%

Pemphigus and thyroid disease: A systematic review and meta-analysis

et al. 2023

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Objective No consensus exists regarding the association between pemphigus and thyroid disease. To explore the relationship between the two conditions by synthesizing the existing data. Methods We performed this review based on PubMed, Embase and Web of Science (from inception to 2022) and used the Newcastle-Ottawa scale for assessing the quality of studies. The outcome was represented by pooled odds ratios (ORs) with 95% confidence intervals (CI). And the publication bias and sensitivity analyses were developed. Results Our analyze finally included six studies containing 17,567 pemphigus patients. Overall, we revealed that pemphigus is significantly associated with hypothyroidism (OR 1.70, 95% CI 1.54–1.87), while not with thyroid cancer (OR 0.93, 95% CI 0.41–2.11) and autoimmune thyroid disease (AITD) (OR 1.64, 95% CI 0.91–2.95). In subgroup analyses, pemphigus was also not associated with Graves’ disease (OR 0.97, 95% CI 0.63–1.49) and Hashimoto’s thyroiditis (OR 1.32, 95% CI 0.88–1.97). Conclusion Our results reveal a significant association between pemphigus and hypothyroidism. Considering other relevant studies, we also speculate that the prevalence of AITD is higher in pemphigus patients than in the general population.

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Serum Detection of Anti-thyroid Peroxidase and Anti-thyroglobulin Antibodies in Chinese Patients With Pemphigus Vulgaris and Pemphigus Foliaceus and Literature Review

Cited by 4 publications

References 30 publications

Desmoglein compensation hypothesis fidelity assessment in Pemphigus

Desmoglein compensation hypothesis fidelity assessment in Pemphigus

Patient genetics shape the autoimmune response in the blistering skin disease pemphigus vulgaris

Pemphigus and thyroid disease: A systematic review and meta-analysis

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