The use of C3d and C4d immunohistochemistry on formalin-fixed tissue as a diagnostic adjunct in the assessment of inflammatory skin disease

Magro, Cynthia M.; Dyrsen, Molly E.

doi:10.1016/j.jaad.2008.06.022

Cited by 61 publications

(86 citation statements)

References 43 publications

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“…We didn't find these patterns in the controls, with the exception of some even, nonspecific staining of IgG and IgM within the dermis. Other authors have reported studies utilizing IHCs in ABD diagnosis, with similar results to ours in the classical patterns [14][15][16][17]. Our non-classic patterns of positivity have been also documented in DIF and IIF, especially when using multicolor and confocal microscopy (not routinely utilized in most immnodermatopathology laboratories).…”

Section: Followed the Same Pattern As Fibrinogensupporting

confidence: 88%

Immunohistochemistry versus immunofluoresence in the diagnosis of autoimmune blistering diseases

Velez¹,

Howard²

2013

Our Dermatol Online

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Introduction: In patients with autoimmune skin blistering diseases (ABDs), the diagnostic gold standard has classically been direct and indirect immunofluorescence (DIF and IIF), despite inherent technical problems of autofluorescence. Aim: We sought to overcome autofluorescence issues and compare the reliability of immunofluorescence versus immunohistochemistry (IHC) staining in the diagnoses of these diseases. Methods: We tested via IHC for anti-human IgG, IgM, IgA, IgD, IgE, Kappa light chains, Lambda light chains, Complement/C3c, Complement/ C1q, Complement/C3d, albumin and fibrinogen in 30 patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF), and 30 control biopsies from the endemic area. We also tested archival biopsies from patients with ABDs whose diagnoses were made clinically, histopathologically and by DIF/IIF studies from 2 independent dermatopathology laboratories in the USA. Specifically, we tested 34 patients with bullous pemphigoid (BP), 18 with pemphigus vulgaris (PV), 8 with pemphigus foliaceus (PF), 14 with dermatitis herpetiformis (DH) and 30 control skin samples from plastic esthetic surgery reduction surgeries. Results: The diagnostic correlation between IHC and DIF-IIF was almost 98% in most cases. IHC revealed evidence of autofluorescence around dermal blood vessels, dermal eccrine glands and neurovascular packages feeding skin appendices in ABDs; this autofluorescence may represent a non-specific immune response. Strong patterns of positivity were seen also in endothelial-mesenchymal cell junction-like structures, as well as between dermal fibrohistiocytic cells. In PV, we noted strong reactivity to neurovascular packages supplying sebaceous glands, as well as apocrine glands with edematous changes. Conclusions:We suggest that IHC is as reliable as DIF or IIF for the diagnosis of ABDs; our findings further suggest that what has previously been considered DIF/IIF autofluorescence background may be of relevance in ABDs. Our discovery of reactivity against edematous dermal apocrine glands may be related to the fact that PV has a vegetant form, with lesions present in anatomic areas where these glands exist.

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Section: Followed the Same Pattern As Fibrinogensupporting

confidence: 88%

Immunohistochemistry versus immunofluoresence in the diagnosis of autoimmune blistering diseases

Velez¹,

Howard²

2013

Our Dermatol Online

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“…C4d is a stable component of classical complement activation and represents a degradation product of C4b 19. C3d is also a stable component of complement activation, although it can be formed in both classical or alternative complement activation 19. As shown by Magro and Dyrsen,19 all DLE cases showed granular, moderate to marked intensity C3d deposits at DEJ, whereas C4d deposits were found in only 15% of DLE patients.…”

Section: Other Staining Methods In Lementioning

confidence: 96%

Section: Other Staining Methods In Lementioning

confidence: 99%

The lupus band test in systemic lupus erythematosus patients

Reich¹,

Marcinow²,

Białynicki‐Birula³

2011

TCRM

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The lupus band test (LBT) is a diagnostic procedure that is used to detect deposits of immunoglobulins and complement components along the dermoepidermal junction in patients with lupus erythematosus (LE). The LBT is positive in about 70%–80% of sun-exposed non-lesional skin specimens obtained from patients with systemic LE (SLE), and in about 55% of SLE cases if sun-protected nonlesional skin is analyzed. In patients with cutaneous LE only, the lesional skin usually shows a positive LBT. The LBT helps in differentiating LE from other similar skin conditions and may also be helpful in making the diagnosis of SLE in subjects with no specific cutaneous lesions. Furthermore, a positive LBT may be applied as a prognostic parameter for LE patients. However, the correct interpretation of this test requires detailed knowledge of the site of the biopsy, deposit components, morphology and brightness of the immunofluorescent band, and other associated serologic findings, as well as the response to treatment. It must be emphasized that LBT is a laboratory procedure that should always be interpreted in conjunction with clinical findings and other serological and immunopathological parameters.

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“…1,2 More recently, commercially available mouse monoclonal and rabbit polyclonal antibodies have been produced that are able to reliably detect human C3d and C4d, stable component of classic complement activation, on FFPE biopsies using immunoenzymatic techniques. The usefulness of immunohistochemical detection (IHC) of C3d and C4d in the diagnosis of inflammatory dermatoses, including AIBD, has been addressed in some studies [3][4][5][6] ; these included a limited number of biopsies or studied a variety of inflammatory dermatoses without targeting specifically AIBD, and their results were sometimes contradictory. 6 The purpose of this study was to further assess the usefulness of immunoperoxidase detection of C4d in FFPE skin specimens in the diagnosis of BP and P.…”

Section: Introductionmentioning

confidence: 99%

Application of C4d Immunohistochemistry on Routinely Processed Tissue Sections for the Diagnosis of Autoimmune Bullous Dermatoses

Villani

Chouvet

Kanitakis

2016

The American Journal of Dermatopathology

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The diagnosis of autoimmune bullous dermatoses relies greatly on direct immunofluorescence (DIF) examination performed on frozen tissue sections, showing deposits of immunoglobulins and/or C3 on specific cutaneous structures. However, frozen material is not always available for DIF; therefore, alternative techniques are needed in the diagnostic procedure. We therefore tested the usefulness of C4d immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections for the diagnosis of bullous pemphigoid (BP) and pemphigus (P). A retrospective immunohistochemical study was performed on biopsies of BP (n: 29) and P (n: 22, including 19 Pemphigus vulgaris and 3 paraneoplastic), submitted for routine histological examination and compared with DIF on the corresponding frozen sections. Twenty-five BP biopsies (86.2%) showed C4d deposits seen as a linear labeling along the dermal-epidermal junction and on the membrane of basal keratinocytes. Seventeen P biopsies (77.2%) showed C4d deposits in a classical "intercellular" pattern, predominating on the lower epidermal layers. The sensitivity, specificity, positive predictive value, and negative predictive value reached 86%, 98%, 96%, and 92% in BP, respectively and 77%, 98%, 94%, and 92% in P, respectively. Furthermore, in the cases where serological tests were available, the sensitivity of C4d detection was higher than that of enzyme-linked immunosorbent assay/indirect immunofluorescence in both BP (87% vs. 67%) and P (82% vs. 54.5%). We conclude that DIF on frozen sections still remains the gold standard for the immunopathological diagnosis of BP and P; however, in the absence of frozen material, C4d immunohistochemistry performed on routinely processed biopsy material can be of considerable help in confirming the diagnosis.

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The use of C3d and C4d immunohistochemistry on formalin-fixed tissue as a diagnostic adjunct in the assessment of inflammatory skin disease

Cited by 61 publications

References 43 publications

Immunohistochemistry versus immunofluoresence in the diagnosis of autoimmune blistering diseases

Immunohistochemistry versus immunofluoresence in the diagnosis of autoimmune blistering diseases

The lupus band test in systemic lupus erythematosus patients

Application of C4d Immunohistochemistry on Routinely Processed Tissue Sections for the Diagnosis of Autoimmune Bullous Dermatoses

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