Yoshie Kawahara

Subepidermal blistering disease with autoantibodies against a novel dermal 200-kDa antigen

A number of autoimmune subepidermal blistering diseases are characterized by the distinct autoantigens of the cutaneous basement membrane zone. Recently, a few cases with autoantibodies against a novel 200-kDa dermal protein have been reported. We collected nine cases of subepidermal blistering disease with IgG antibodies against this 200-kDa antigen. In this report, we describe the clinical and immunological appearances in these cases. Five cases showed bullous pemphigoid-like features, one case resembled dermatitis herpetiformis, and another case showed mixed features of bullous pemphigoid and linear IgA bullous dermatosis. It was interesting to note that psoriasis coexisted in four cases. By indirect immunofluorescence on 1 M NaCl split skin, IgG antibodies from all sera reacted with the dermal side of the split. By immunoblot analysis, IgG antibodies recognized a 200-kDa protein of dermal extract. IgG affinity-purified antibodies on the 200-kDa immunoblot membrane stained the dermal side of 1 M NaCl split skin. Various examinations suggested that the 200-kDa antigen is not identical to any chains of laminins-1, -5 or -6. This autoimmune subepidermal blistering disease against the dermal 200-kDa protein may form a new distinct entity, which often associates with psoriasis.

Spectrum and clinical significance of autoantibodies against transfer RNA

OBJECTIVE To characterize the clinical features of patients who have autoantibodies against transfer RNA (tRNA) or tRNA-associated proteins. METHODS Sera from 1,472 patients with suspected systemic rheumatic disease were screened by RNA immunoprecipitation of HeLa cell extracts. The specificities of the antibodies that precipitated tRNAs were further analyzed by immunoprecipitation using deproteinized RNAs and 35S-methionine-labeled HeLa cell extracts, followed by immunoblotting. RESULTS Forty-one serum samples (2.8%) were found to immunoprecipitate tRNAs. Thirteen patients were identified as having previously defined anti-aminoacyl-tRNA synthetase antibodies (anti-histidyl-tRNA synthetase in 4 patients, anti-threonyl-tRNA synthetase in 1, anti-alanyl-tRNA synthetase in 3, anti-glycyl-tRNA synthetase in 4, and anti-isoleucyl-tRNA synthetase in 1). All 13 patients had myositis and/or interstitial pneumonitis. Sera from the remaining 28 patients immunoprecipitated previously unidentified tRNAs, including 13 serum samples that bound deproteinized cognate tRNA; 24 of the 28 patients met criteria for either systemic lupus erythematosus (SLE) or Sjögrens syndrome (SS). In addition, nonerosive polyarthritis, leukocytopenia, rheumatoid factor, and characteristic annular or papulosquamous recurrent erythema were noted in these patients; however, renal involvement was rare. Sera from 16 of these 28 patients also contained anti-Ro/SSA and/or anti-La/SSB antibodies. While 189 patient sera precipitated Ro/SSA and/or La/SSB-associated RNAs but not tRNA, only 12 of the patients (6.3%) developed skin lesions (P=0.0009, odds ratio 8.85). CONCLUSION Novel autoantibodies against tRNAs or tRNA-associated proteins were identified in 28 sera. These autoantibodies appear to be distinct from anti-aminoacyl-tRNA synthetase antibodies and are associated with SLE and SS. The presence of anti-Ro/SSA and/or anti-La/SSB along with anti-tRNA antibodies is more strongly associated with recurrent erythema than is the presence of anti-Ro/SSA or anti-La/SSB alone.

A Case of Unique Subepidermal Blistering Disease with Autoantibodies against a Novel Dermal 200-kD Antigen

Background: Several autoimmune subepidermal blistering diseases with autoantibodies against the epidermal basement membrane zone (BMZ) have been identified. Each shows distinct immunological findings. Objectives: Our patient showed clinical features which were indicative of bullous pemphigoid or linear IgA bullous dermatosis. In his serum, circulating IgG antibodies binding to the dermal side of skin split with 1 M NaCl were detected. To clarify the immunological character of the patient, we performed further studies. Methods: Western immunoblot analysis using normal human skin extracts and indirect immunofluorescence (IF) with affinity-purified IgG antibodies to the detected dermal protein were done. Results: Western immunoblot analysis demonstrated IgG antibodies reacting with a dermal 200-kD protein. Affinity-purified IgG antibodies to the 200-kD protein reacted to the dermal side of the split by indirect IF. Therefore, this dermal 200-kD protein is believed to be the epidermal BMZ antigen. Conclusion: Our patient showed an immunologically unique subepidermal blistering disease.

Spectrum of cutaneous vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): a case series.

Background:The diverse histopathologic spectrum of cutaneous vasculitis in eosinophilic granulomatosis with polyangiitis (EGPA, Churg–Strauss syndrome) has not been well described. Methods:Fifteen skin biopsy specimens from 9 EGPA patients with histopathologically proven necrotizing vasculitis were reviewed clinicopathologically. Results:Among 8 patients with dermal small vessel vasculitis, neutrophilic vasculitis was observed in 2 myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)–positive patients, whereas the remaining 6 MPO-ANCA–negative patients showed eosinophilic vasculitis in 3 and a mixed infiltrate of neutrophils and eosinophils in another 3 patients. Five patients with muscular vessel vasculitis showed vasculitis at different inflammatory stages in separate or coexisting at the same biopsied skin lesions: acute stage (eosinophilic vasculitis), granulomatous stage (granulomatous vasculitis), and healed stage. Coexistent small vessel and muscular vessel vasculitis was found in 4 patients. Conclusions:The histopathologic spectrum of dermal small vessel vasculitis in EGPA ranges from eosinophilic vasculitis with negative MPO-ANCA at one end to neutrophilic vasculitis with positive MPO-ANCA at the other end. The affected vessels ranging from dermal small vessels to subcutaneous muscular vessels in addition to the MPO-ANCA phenotype may account for the many facets of vasculitis in EGPA.

Two Cases of Atypical Bullous Disease Showing Linear IgG and IgA Deposition in the Basement Membrane Zone

Patients showing coexistent linear IgG and IgA deposition along the basement membrane zone on direct immunofluorescence have been described as either bullous pemphigoid, epidermolysis bullosa acquisita, linear IgA bullous dermatosis, or cicatricial pemphigoid, depending on the clinical features and laboratory findings. In the present report, we describe two cases showing atypical clinical features distinct from those of other known bullous diseases. No circulating antibodies were detected by indirect immunofluorescence of normal human skin. Indirect immunofluorescence of 1 M NaCl split skin revealed IgG and/or IgA antibodies reactive with the dermal side of the split. Immunoblotting of normal human epidermal and dermal extracts showed no apparent reactivity with known autoantigens. The results suggest that there may be a unique and distinct bullous disease with linear IgG and IgA deposition at the basement membrane zone.

Multiple ulcers on the face due to infection after thread-lifting

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