Serum autoantibodies against the extracellular region of α6β4 integrin in a patient with dipeptidyl peptidase-4 inhibitor–induced bullous pemphigoid

Yamashita, Chigusa; Arase, Noriko; Higuchi, Shuhei; Arase, Hisashi; Takagi, Junichi; Nojima, Satoshi; Tanemura, Atsushi; Fujimoto, Manabu

doi:10.1016/j.jdcr.2021.12.021

Cited by 4 publications

(6 citation statements)

References 10 publications

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“…These three were also positive for both anti‐BP180 extracellular region and anti‐BP180 NC16A antibodies, and two of them were receiving DPP‐4 inhibitors (Figure 1a; Table S2). 5 …”

Section: Resultsmentioning

confidence: 99%

“…Cells expressing the α6β4 integrin were stained with sera diluted 100-fold from 20 pemphigoid patients treated at our hospital and from 20 healthy subjects and analysed by flow cytometry to detect autoantibodies to the extracellular region of α6β4. 5,19 Autoantibodies to the extracellular region of BP180, including NC16A and the C-terminus of BP180, were similarly analysed. 19,20 The 99th percentile tile values for healthy subjects were 0 U for the anti-α6β4 integrin antibody and 33.8 U for the anti-BP180 antibody.…”

Section: Autoantibodies Against α6β4 Integrin In Patients With Pemphi...mentioning

confidence: 99%

“…Mean fluorescence intensities (MFI) for the integrin-expressing (GFP-positive) and non-expressing (GFP-negative) cells were analysed by FACS Celesta (BD, USA), and the differences in MFI were calculated and used as the antibody titres. 5 In some experiments, cells expressing α6β4 integrin were stained with a monoclonal antibody against β4 integrin of serial dilutions, and the MFI at a concentration of 1 μg/mL of antibody was defined as 100 U. A standard curve was generated and autoantibody levels were expressed in arbitrary units.…”

Section: Autoantibody Assaysmentioning

confidence: 99%

“…Anti‐α6 and/or anti‐β4 integrin antibodies have been found in certain patients with mucous membrane pemphigoid (MMP), 1–3 with autoantibodies against the intracellular region of the β4 integrin detected in some patients with ocular MMP 3,4 . On the other hand, we have recently seen a patient with DPP‐4 inhibitor‐induced bullous pemphigoid who had autoantibodies against the extracellular region of the α6β4 integrin complex expressed on the cell surface 5 . However, it remains unclear whether and how these anti‐α6β4 integrin antibodies affect patients with pemphigoid.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 On the other hand, we have recently seen a patient with DPP-4 inhibitor-induced bullous pemphigoid who had autoantibodies against the extracellular region of the α6β4 integrin complex expressed on the cell surface. 5 However, it remains unclear whether and how these anti-α6β4 integrin antibodies affect patients with pemphigoid.…”

Section: Introductionmentioning

confidence: 99%

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Anti‐α6β4 integrin autoantibodies inhibit the binding of laminins to α6β4 integrin in patients with pemphigoid and affect the gastrointestinal tract

Arase,

Sasaoka,

Narita

et al. 2023

Acad Dermatol Venereol

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BackgroundAnti‐α6β4 integrin autoantibodies can be observed in some patients with mucous membrane pemphigoid. We have previously identified anti‐α6β4 integrin extracellular domain autoantibodies together with anti‐BP180 NC16A antibodies in a patient with DPP‐4 inhibitor‐induced bullous pemphigoid. However, the significance and impact of anti‐α6β4 integrin antibodies are unknown.ObjectivesTo characterize anti‐α6β4 integrin extracellular domain autoantibodies in pemphigoid patients, to determine whether these antibodies inhibit laminin‐α6β4 integrin binding and to observe their systemic effects.MethodsAnti‐α6β4 integrin autoantibodies were analyzed by staining cells expressing the extracellular region of α6β4 integrin with sera from 20 patients with pemphigoid. The anti‐α6β4 integrin autoantibodies were characterized using different transfectants. The binding of laminins to α6β4 integrin was studied using cells expressing the activated conformation of α6β4 integrin and the inhibitory effect of the autoantibodies on the binding of laminins to α6β4 integrin was tested. Trends in antibody titers and clinical symptoms were quantified and analyzed.ResultsIgG autoantibodies against the extracellular domain of anti‐α6β4 integrin were found in some patients with pemphigoid. Laminin binding to α6β4 integrin was observed in the active conformation of α6β4 integrin, and serum from a patient with a high titer of anti‐α6β4 integrin antibodies inhibited the binding of both laminin‐511 and laminin‐332 to α6β4 integrin. α6β4 integrin is expressed on the basement membrane of both skin and small intestine, and exfoliation was observed in the patient's epidermis and small intestinal epithelium. A reduction in the titer of the anti‐α6β4 integrin antibody was associated with improvement in both skin and gastrointestinal symptoms.ConclusionsThis study demonstrated the presence of anti‐α6β4 integrin extracellular domain‐specific autoantibodies in some patients with pemphigoid. In addition, these autoantibodies showed inhibitory activity on α6β4 integrin‐laminin binding. Anti‐α6β4 integrin antibodies can affect the gastrointestinal tract as well as the skin and oral mucosa.

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“…These three were also positive for both anti‐BP180 extracellular region and anti‐BP180 NC16A antibodies, and two of them were receiving DPP‐4 inhibitors (Figure 1a; Table S2). 5 …”

Section: Resultsmentioning

confidence: 99%