Clinical and immunological findings in 55 patients with anti‐laminin 332‐type mucous membrane pemphigoid

Li, X; Qian, Hua; Natsuaki, Yohei; Koga, Hiroshi; Kawakami, Tamihiro; Tateishi, Chiharu; Tsuruta, Daisuke; Ishii, Norito; Hashimoto, Takashi

doi:10.1111/bjd.20099

Cited by 18 publications

(26 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to oral and ocular mucosal lesions, we collected information for lesions on nasal, pharyngeal, laryngeal, esophageal, and genital mucosae. Furthermore, to evaluate the severities of LM332-MMP, "oral score" (0-5) was calculated by the numbers of involved parts on oral mucosae (i.e., lip, tongue, cheek, gingiva and palate), and "mucosal score" (0-7) was calculated by the number of involved mucosae (i.e., oral, ocular, nasal, pharyngeal, laryngeal, esophageal, and genital mucosae), as we previously reported (12).…”

Section: Patients and The Information For The Clinical Featuresmentioning

confidence: 99%

“…Recently, we have reported a retrospective study of the clinical and immunological findings summarized for 55 LM332-MMP cases, which were diagnosed with very strict inclusion criteria, including positive DIF and the absence of other autoantigens (12). This study indicated that IIF using 1M-NaCl-split normal human skin (ssIIF) is also valuable for the diagnosis of LM332-MMP (12).…”

Section: Introductionmentioning

confidence: 99%

“…As the second version to the previous study (12), in the present study, using new inclusion criteria with positive ssIIF and concurrence of other autoantigens, we selected 133 cases of LM332-MMP from our large AIBD cohort at Kurume University, which included the 55 previous cases. Then, we further assessed in more detail both clinical features and immunological findings in the 133 cases, and extensive statistical analyses were also performed, which suggested that the new criteria are useful for the diagnosis of LM332-MMP.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases

et al. 2021

View full text Add to dashboard Cite

BackgroundRecently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence and absence of antibodies to non-LM332 autoantigens. However, indirect immunofluorescence using 1M-NaCl-split normal human skin (ssIIF) is also valuable for diagnosis of anti-LM332-type MMP.MethodsIn this second study, we selected 133 anti-LM332-type MMP cases, which were diagnosed by our different inclusion criteria: (i) immunoglobulin G (IgG) deposition to basement membrane zone (BMZ) by direct immunofluorescence or IgG reactivity with dermal side of split skin by ssIIF, (ii) positivity for at least one of the three subunits of LM332 by immunoblotting of purified human LM332, and (iii) the presence of mucosal lesions. Clinical, histopathological, and immunological findings were summarized and analyzed statistically. Although these cases included the 55 previous cases, the more detailed study for larger scale of patients was conducted for further characterization.ResultsClinically, among the 133 patients, 89% and 43% patients had oral and ocular mucosal lesions, respectively, 71% had cutaneous lesions, and 17% had associated malignancies. Histopathologically, 93% patients showed subepidermal blisters. The sensitivities of ssIIF and direct immunofluorescence are similar but are significantly higher than indirect immunofluorescence using non-split human skin (both p < 0.001). In immunoblotting of purified LM332, patient IgG antibodies most frequently reacted with LMγ2 subunit (58%), followed by LMα3 (49%) and LMβ3 (36%). Thirty-four percent patients recognized additional non-LM332 autoantigens. Statistical analysis revealed that autoantibodies against non-LM332 autoantigens might stimulate the production of anti-LMγ2 antibodies.ConclusionsThis retrospective study further characterized in more detail the clinical and immunological features of 133 cases of anti-LM332-type MMP, in which the new diagnostic criteria without positive direct immunofluorescence reactivity were useful for the diagnosis. Higher frequency with anti-LMγ2 antibodies suggested more significant pathogenic role of this subunit. Additional autoantibodies to non-LM332 autoantigens detected in one-third of the patients may contribute to complexity in anti-LM332-type MMP, including the induction of anti-LMγ2 antibodies.

show abstract

Section: Patients and The Information For The Clinical Featuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases

et al. 2021

View full text Add to dashboard Cite

show abstract

“…We have identified IgG autoantibodies against the laminin β3 subunit as having the most pro-inflammatory effect, followed by anti-γ2, and anti-α3 laminin. Interestingly, anti-laminin β3 autoantibodies are the least prevalent autoantibodies in laminin-332 pemphigoid ( 6 , 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…Laminin-332 is an extracellular glycoprotein composed of the a3, b3, and g2 subunits with a large G domain at the base containing epidermal growth factor-based repeats (4,5). The a3 subunit is the most frequently targeted subunit in laminin-332 pemphigoid, followed by g2 and b3 (6,7). Laminin-332 pemphigoid has been associated with a more aggressive phenotype and with extensive laryngopharyngeal involvement (6,(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Subunit-Specific Reactivity of Autoantibodies Against Laminin-332 Reveals Direct Inflammatory Mechanisms on Keratinocytes

Bao

Solimani

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Laminin-332 pemphigoid is a rare and severe autoimmune blistering disease, caused by IgG autoantibodies targeting laminin-332 in the dermal-epidermal basement zone. Laminin-332 pemphigoid is characterized by variable inflammatory infiltrate and the predominance of non-complement-fixing antibodies. Given these findings, we hypothesized that IgG autoantibodies to laminin-332 directly resulted in keratinocyte expression of inflammatory factors. We performed RNA-seq on primary human keratinocytes treated with IgG from patients with laminin-332 pemphigoid. Genes for numerous cytokines and chemokines were upregulated, including CSF2, CSF3, CXCL1, CXCL5, CXCL3, CXCL8, CXCL10, CXCL1, IL6, IL7, IL15, IL23, IL32, IL37, TGFB2 as well as metalloproteases. Considering the pro-inflammatory and proteolytic effect of autoantibodies from patients with laminin-332 pemphigoid identified in our initial experiment, we next questioned whether the reactivity against specific laminin subunits dictates the inflammatory and proteolytic keratinocyte response. Then, we treated keratinocytes with IgG from a separate cohort of patients with reactivity against individual subunits of laminin-332. We identified upregulation of IL-1α, IL-6, IL-8, CXCL1, MMP9, TSLP, and GM-CSF at the protein level, most notably in keratinocytes treated with IgG from laminin β3-reactive patients. We for the first time demonstrated a pro-inflammatory response, similar to that described in keratinocytes treated with IgG autoantibodies from patients with bullous pemphigoid, providing novel insight into the pathogenesis of laminin-332 pemphigoid and laminin-332 biology.

show abstract

Evaluation of Site- and Autoantigen-Specific Characteristics of Mucous Membrane Pemphigoid

et al. 2022

View full text Add to dashboard Cite

ucous membrane pemphigoid (MMP) is a rare subepithelial autoimmune bullous disease typified by predominant mucosal involvement and scarring. 1 It poses a substantial diagnostic challenge owing to the generally lower levels of serum autoantibodies compared with other autoimmune bullous diseases. The heterogeneity of autoantigens targeted in MMP, autoantibody isotypes (immunoglobulin [Ig] IgG, IgA, or both), and the lack of widely available serological assays further hamper early recognition of MMP. Given the rarity of the disease, data about the association of clinical and immunopathological features of the disease are limited. The aim of the current study was to investigate the clinical, immunoserological, and immunopathological characteristics of a large cohort of patients with MMP managed in 2 tertiary centers. MethodsWe performed a retrospective cohort study that included routine data from all patients diagnosed with MMP between January 1, 2007, and February 28, 2020, in 2 referral centers for autoimmune bullous diseases at the

show abstract

Clinical and immunological findings in 55 patients with anti‐laminin 332‐type mucous membrane pemphigoid

Cited by 18 publications

References 7 publications

The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases

The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases

Subunit-Specific Reactivity of Autoantibodies Against Laminin-332 Reveals Direct Inflammatory Mechanisms on Keratinocytes

Evaluation of Site- and Autoantigen-Specific Characteristics of Mucous Membrane Pemphigoid

Contact Info

Product

Resources

About