Bullous Pemphigoid: Use of C4d Immunofluorescent Staining in a Case With Repeated Negative Conventional Direct Immunofluorescence Studies

Kassaby, Sarah; Hicks, Alexander; Leicht, Stuart; Youngberg, George A.

doi:10.1097/dad.0000000000000943

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…Although one case report already showed C4d deposition in an IgG/C3c negative case, our study is the first larger case series to investigate the use of C4d detected by DIF in BP. 10…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Utility of C4d by Direct Immunofluorescence in Bullous Pemphigoid

Damman

Edwards

Doorn

et al. 2020

The American Journal of Dermatopathology

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Bullous pemphigoid (BP) is an autoimmune blistering disease that commonly affects elderly patients. Direct immunofluorescence (DIF) for immunoglobulin G (IgG) and C3c on frozen skin biopsies is the gold standard for the diagnosis of BP. In a minority of cases, IgG and/or C3c are found negative, and in these situations, there is a need for a more stable diagnostic marker of BP. C4d is biologically inactive, but has a long half-life, rendering it a longlived marker for antibody-mediated complement activation. Previous studies already demonstrated that C4d was diagnostically useful in formalin-fixed paraffin-embedded skin biopsies of patients with BP. We hypothesized that C4d detected by DIF could also be a promising diagnostic marker for BP, particularly in IgG and/or C3c DIF-negative cases. In this single-center retrospective study, 69 cases of BP were analyzed for linear deposition of C4d; of the 69 cases, n = 26 were IgG+/C3c2, n = 10 IgG+/C3c+, and n = 33 IgG2/C3c2. Results were compared with n = 39 negative controls. Seven of the 26 (27%) IgG+/C3c2 and 3 of the 33 (9%) IgG2/ C3c2 BP cases were positive for C4d. All 10 IgG+/C3c+ cases were also C4d positive. In the negative control group, 2 of the 39 (5%) were found positive for C4d. In conclusion, the current study shows that C4d is a more sensitive but not a 100% specific marker of BP. We conclude that C4d by DIF could be an interesting diagnostic adjunct for BP, particularly in IgG2/C3c2 double negative cases.

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“…Although one case report already showed C4d deposition in an IgG/C3c negative case, our study is the first larger case series to investigate the use of C4d detected by DIF in BP. 10…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Utility of C4d by Direct Immunofluorescence in Bullous Pemphigoid

Damman

Edwards

Doorn

et al. 2020

The American Journal of Dermatopathology

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“…Additionally, IHC C4d had a lower positive predictive value than IHC C3d (24.1% vs. 90.9%). Kassaby et al 18 reported a case with negative C3d result and positive C4d result via DIF and IHC studies. They demonstrated that C4d is more stable and persistent in tissue than C3d, as the C4d complement fragment bind covalently to endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Bullous pemphigoid diagnosis: the role of routine formalin-fixed paraffin-embedded skin tissue immunochemistry

Kim

Lee

2022

Sci Rep

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The gold standard for diagnosing bullous pemphigoid (BP) is the detection of linear deposition of IgG and/or C3 at the dermoepidermal junction using direct immunofluorescence (DIF). Because DIF has several disadvantages, primarily the requirement for frozen specimens, we assessed the diagnostic value of immunohistochemical (IHC) staining for BP detection. Eighty-eight patients with bullous lesions were included in this study. IHC staining for C3d, C4d, and IgG was performed on 88 samples, which included specimens from patients with DIF-confirmed BP (n = 43), clinicopathologically suspected BP with negative DIF results (n = 9), and other bullous diseases (n = 36). Diagnosis based on positive results for C3d, C4d, or IgG in IHC staining detected 86% of DIF-confirmed BP cases. The sensitivity of IHC staining for the detection of DIF-confirmed BP cases and clinicopathologically suspected BP cases was similar to that of DIF (80.8% vs. 84.3%), but the specificity was higher (83.3% vs. 75.0%). Five of the nine clinicopathologically suspected BP cases were diagnosed using IHC staining. Thus, IHC staining of routine biopsy material could be an alternative method for diagnosing BP. IHC staining has considerable diagnostic potential, especially in cases with a high suspicion of BP, but negative or suboptimal DIF results.Please check and confirm the author names and initials are correct. Author 2: Given name: [Chul Hwan] Family name: [Kim], Author 3: Given name: [Yoo Jin] Family name: [Lee].Checked it.

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“…A reliable technique of IHC for IgA and IgG on FFPE tissue needs to be established to obtain higher sensitivity. Moreover, a case reported that DIF for C4d may be useful for BP in the case of negative results of DIF for IgG and C3 …”

Section: Immunological Methodsmentioning

confidence: 99%

“…Moreover, a case reported that DIF for C4d may be useful for BP in the case of negative results of DIF for IgG and C3. 14 DIF samples stored in normal saline for transportation within 24 h may be optimal, because of reduction in IgG background fluorescence and enhancement of desired specific staining. 15 Michel's fixative, liquid nitrogen and saline are used for longer transportation periods of 24-48 h (liquid nitrogen for transportation presents a potential danger).…”

Section: Direct Immunofluorescencementioning

confidence: 99%