title: Cutaneous vascular deposition of C5b-9 and its role as a diagnostic adjunct in the setting of diabetes mellitus and porphyria cutanea tarda.
abstract: BACKGROUND
  The cutaneous lesions of diabetes mellitus (DM) and porphyria cutanea tarda (PCT) exhibit distinctive microvascular changes including basement membrane zone thickening and lamellation, morphologically appearing as hyaline-like alterations of the vessel wall. Immunofluorescence demonstrates homogeneous mantles of immunoglobulin in the microvasculature. The staining intensity is variable and in some cases can closely approximate those immunofluorescent changes seen in photoaged skin.
  
  
  OBJECTIVE
  The purpose of this study was to establish an association between the microvascular changes seen in the skin from patients with DM and PCT and the presence of C5b-9 deposition, potentially defining the C5b-9 assay as an additional diagnostic adjunct.
  
  
  METHODS
  Routine light microscopy and immunofluorescence studies were conducted on skin biopsy specimens from 14 patients with cutaneous manifestations of DM and 17 patients with PCT. The immunofluorescence profile included IgG, IgM, IgA, C3, C3d, C4d, and C5b-9.
  
  
  RESULTS
  Fourteen of 14 DM and 17 of 17 PCT skin biopsy specimens revealed extensive granular and homogeneous vascular deposition of C5b-9; a similar pattern was observed for C3d and C4d. Control specimens from patients without DM and PCT, where C5b-9 was not an expected immunoreactant, were negative. Positive controls were cases of vasculitis, scleroderma, and dermatomyositis without DM and PCT where C5b-9 deposition was expected. C5b-9 deposition was observed and was of lesser magnitude than that encountered in patients with PCT or DM.
  
  
  CONCLUSIONS
  We were unable to obtain detailed clinical information on some of the diabetic patients in regards to significant extracutaneous vascular complications. In addition, a correlation between hemoglobin 1 Ac levels and the extent of C5b-9 deposition could not be ascertained as the serum levels for hemoglobin 1 Ac were unknown.
  
  
  CONCLUSIONS
  Granular and homogeneous deposits of C5b-9 in vessels, along with homogeneous deposits of immunoglobulin within the blood vessels, are characteristic immunofluorescence findings in patients with DM and PCT. In regards to potential mechanisms of C5b-9 deposition, decreased metabolism of C5b-9 due to glycosylation of CD59 in the setting of DM and activation of complement by irradiated porphyrins in PCT are proposed. The extent of C5b-9 deposition suggests that this complex may play a pathogenetic role in the evolution of microvascular injury in patients with DM and PCT.
authors.affiliation: Ohio State University College of Medicine and Public Health, Columbus, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Vasil
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Magro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003176:Complement C3 / Q000032:analysis; D003179:Complement C3b / Q000032:analysis; D015933:Complement C3d / Q000032:analysis; D015935:Complement C4b / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis*; D048909:Diabetes Complications / Q000276:immunology* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000276:immunology / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006031:Glycosylation; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D017119:Porphyria Cutanea Tarda / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000098:blood supply / Q000737:chemistry / Q000276:immunology*
chemical_list: D003176:Complement C3; D003179:Complement C3b; D015933:Complement C3d; D015935:Complement C4b; D015938:Complement Membrane Attack Complex; D006442:Glycated Hemoglobin; D007136:Immunoglobulins; D010446:Peptide Fragments; C032261:complement C4d