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Vancomycin Mediates IgA Autoreactivity in Drug-Induced Linear IgA Bullous Dermatosis.

ABSTRACT: Vancomycin (VCM) is known to induce linear IgA bullous dermatosis (LAD). However, in contrast to conventional LAD, in which circulating IgA autoantibodies against basement membrane proteins are commonly detected, patient sera from VCM-induced LAD yields negative results in indirect immunofluorescence microscopy, and the targeted autoantigen remains undetermined. By using sera from a typical patient with VCM-induced LAD, we identified that co-incubation of sera with VCM resulted in linear IgA deposition at the basement membrane zone by indirect immunofluorescence. Patient sera reacted with the dermal side of 1 mol/L NaCl-split skin and with the recombinant noncollagenous (i.e., NC1) domain of type VII collagen by both immunoblot and ELISA in the presence of VCM. The investigation of an additional 13 patients with VCM-induced LAD showed that 10 out of the 14 sera (71.4%) reacted with the NC1 domain of type VII collagen by ELISA when spiked with VCM, whereas only 4 (28.6%) tested positive without it. The enhancement of reactivity to NC1 by VCM, as determined by optical density via ELISA, was observed in 10 out of the 14 sera (71.4%). These findings indicate that type VII collagen is a target autoantigen in VCM-induced LAD and that VCM mediates IgA autoreactivity against type VII collagen, providing an insight into mechanisms involved in drug-induced autoimmune disease.

SUBMITTER: Yamagami J

PROVIDER: S-EPMC8054301 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceNeonatal linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare disease that can be fatal when associated with respiratory failure. All previously reported cases of neonatal LABD have been in newborns with healthy asymptomatic mothers, and the pathogenic IgA was of unknown origin.ObjectiveTo clarify the origin of IgA associated with LABD in neonates born of healthy asymptomatic mothers.Design, setting, and participantsThis case study analyzed the laboratory findings of a single breast-fed newborn male with neonatal LABD admitted to the Keio University Hospital in Tokyo and his healthy asymptomatic mother. The healthy newborn developed life-threatening blisters and erosions of the skin and mucous membranes on day 4 after birth. Blood serum, skin, and maternal breast milk were examined for IgA autoantibodies.Main outcomes and measuresHistopathologic and immunofluorescence analyses of specimens (serum, skin, and breast milk) from the patient and his mother.ResultsHistopathologic evaluation of the newborn's skin revealed subepidermal blisters with neutrophil infiltrates, and immunofluorescence testing showed linear IgA deposition along the basement membrane zone (BMZ), which lead to the diagnosis of neonatal LABD. Indirect immunofluorescence using normal human skin after treatment with 1-mol/L sodium chloride showed the patient to have circulating IgA binding to the dermal side of BMZ. Immunohistochemical staining proved the deposition of secretory IgA in the neonatal skin by demonstrating the presence of J chain-not been seen in other LABD cases-indicating that the autoantibodies producing the blisters were derived from the maternal breast milk. Although no circulating IgA against the skin was detected in mother's sera, the breast milk contained IgA that reacted with the dermal side of the BMZ. No new blister formation was observed after cessation of breastfeeding.Conclusions and relevanceThe results of this case study suggest a passive transfer of pathogenic IgA to a newborn from an asymptomatic mother via breast milk. In prior reports, no serum from asymptomatic mothers of newborns with LABD had IgA autoantibodies binding to skin components; however, in this case, we found that the maternal breast milk contained IgA autoantibodies associated with neonatal LABD. In neonatal LABD, maternal breast milk should be examined for IgA autoantibodies and breast milk feeding should be discontinued as soon as neonatal LABD is suspected.

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Vancomycin Mediates IgA Autoreactivity in Drug-Induced Linear IgA Bullous Dermatosis.

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