Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;49(4):358-362.
doi: 10.1111/cup.14176. Epub 2021 Dec 20.

Impact of adding an IgG4 conjugate to routine direct immunofluorescence testing for subepithelial and intraepithelial autoimmune blistering disorders

Julia S Lehman  1   2   3 , Emma F Johnson  1   2   3 , Michael J Camilleri  1   2   3 , Lawrence E Gibson  1   2   3 , Nneka I Comfere  1   2   3 , Amer N Kalaaji  1   2   3 , Margot S Peters  1   2   3 , Derek J Cervenka  1   2 , Joseph M Doppler  1   2 , Colleen R Lange  1   2 , Cameron J Miller  1   2 , Carilyn N Wieland  1   2   3
Affiliations

Impact of adding an IgG4 conjugate to routine direct immunofluorescence testing for subepithelial and intraepithelial autoimmune blistering disorders

Julia S Lehman et al. J Cutan Pathol. 2022 Apr.

Abstract

Background: Certain autoimmune bullous dermatoses are mediated by autoantibodies of the IgG4 subclass. We determined the diagnostic impact of adding IgG4 to our conventional direct immunofluorescence (DIF) panel.

Methods: For all cases submitted to our referral laboratory for DIF over 1 month (n = 630), we performed IgG4 testing and collected consecutive biopsy specimens showing definite or indeterminate linear or cell-surface deposition of IgG, IgG4, and/or C3. On retrospective blinded review, we classified the pattern and whether the findings were definite, indeterminate, or negative. When present, substantial background staining was recorded.

Results: Seventy DIF specimens met the inclusion criteria. Of 22 (31.4%) specimens equivocal for linear or cell-surface deposition, 9 (40.9%) had definitive IgG4 findings, either linear (3 of 14 equivocal linear cases; 21.4%) or cell-surface (6 of 8 equivocal cell-surface cases; 75.0%). Background deposition was substantial in 14 cases (20.0%) for IgG but in none for C3 or IgG4.

Conclusion: IgG4 allowed the classification of over 40% of DIF cases that were otherwise equivocal by IgG and C3. IgG4 staining showed lower levels of non-specific background staining than IgG or C3. IgG4 appears to contribute most value in cases with cell-surface deposition or with equivocal linear IgG deposition and negative C3 results.

Keywords: complement; direct immunofluorescence; immunobullous disease; immunoglobulin; immunology; pemphigoid; pemphigus.

PubMed Disclaimer

References

REFERENCES

    1. Dainichi T, Chow Z, Kabashima K. IgG4, complement, and the mechanisms of blister formation in pemphigus and bullous pemphigoid. J Dermatol Sci. 2017;88(3):265-270.
    1. Geisler AN, Phillips GS, Barrios DM, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020;83(5):1255-1268.
    1. Zuo Y, Evangelista F, Culton D, et al. IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid. J Autoimmun. 2016;73:111-119.
    1. Lamb PM, Patton T, Deng JS. The predominance of IgG4 in prodromal bullous pemphigoid. Int J Dermatol. 2008;47(2):150-153.
    1. Mihai S, Chiriac MT, Herrero-González JE, et al. IgG4 autoantibodies induce dermal-epidermal separation. J Cell Mol Med. 2007;11(5):1117-1128.

LinkOut - more resources