065
Test #
Alpha-2-Macroglobulin-Like Protein 1 (A2ML1) Immunoblot
CPT Code(s) #
84182
If Profile, Includes Tests:
Disease Name:
Paraneoplastic Pemphigus
Type of Study:
Immunoblot
Methodology:
Western blot
Substrate:
A2ML1 antigen
Reference Range:
Qualitative - Positive or Negative
Units:
N/A
Schedule:
Assay performed once every month.
Specimen Requirements:
Collect 2-5 ml of blood in a red top Vacutainer or serum separator (SST) tube, allow blood to clot, and centrifuge. Label tube appropriately.
Sample Stability:
Room temperature = stable during shipment up to a week
2ºC to 8ºC = 15 days
-15˚C to -25 ºC = Samples that may require prolonged storage (beyond one week).
DO NOT freeze thaw more than once.
Clinical Relevance:
Paraneoplastic pemphigus (PNP) is a rare and life-threatening autoimmune bullous disease that classically occurs in the setting of an underlying neoplasm. Due to the variable disease characteristics and lack of formally accepted diagnostic criteria, PNP remains a diagnostic challenge for clinicians.(1-5) The original diagnostic criteria proposed by Anhalt et al,(6) who first described PNP in 1990, are based on five key clinical, histopathologic, and immunologic features. Subsequent attempts at revising these diagnostic guidelines have been made. Currently, the most referenced diagnostic criteria devised by Camisa and Helm in 1993 consist of a set of major and minor criteria.(7) The diagnosis of PNP requires three major criteria or two major and two minor criteria to be met. However, these diagnostic criteria from 1993 may fail to capture a significant portion of PNP cases. For instance, up to 30% of cases are reported to occur prior to the diagnosis of malignancy. (1,5,8)
The major criteria include (a) mucous membrane lesions with or without cutaneous involvement, (b) concomitant internal neoplasm, and (b) serologic evidence of anti-plakin antibodies including A2ML1. The minor criteria include (a) acantholysis and/or lichenoid interface dermatitis on histopathology and (b) direct immunofluorescence staining showing intercellular and/or basement membrane staining.(9)
Rat bladder indirect immunofluorescence (IIF) studies, are routinely recommended for an easy and rapid diagnosis of PNP, are unable to detect A2ML1 and plakin antibodies in PNP. Internal studies have shown that by combining the RBE, intercellular staining, envoplakin, and A2MLI the sensitivity and specificity of the assay approached 100% for diagnosis of PNP.
References:
1. Paolino G, Didona D, Magliulo G, et al. Paraneoplastic pemphigus: insight into the autoimmune pathogenesis, clinical features and therapy. Int J Mol Sci. 2017;18(12):2532.
2. Maruta CW, Miyamoto D, Aoki V, Carvalho RGR, Cunha BM, Santi CG. Paraneoplastic pemphigus: a clinical, laboratorial, and therapeutic overview. An Bras Dermatol. 2019;94(4):388-398.
3. Lonowski S, Goldbach H, Holland V. Atypical laboratory presentation of paraneoplastic pemphigus associated with Castleman disease. JAAD Case Rep. 2017;3(2):138-139.
4. Didona D, Fania L, Didona B, Eming R, Hertl M, Di Zenzo G. Paraneoplastic dermatoses: a brief general review and an extensive analysis of paraneoplastic pemphigus and paraneoplastic dermatomyositis. Int J Mol Sci. 2020;21(6):2178.
5. Kim JH, Kim SC. Paraneoplastic pemphigus: paraneoplastic autoimmune disease of the skin and mucosa. Front Immunol. 2019;10:1259.
6. Anhalt GJ, Kim SC, Stanley JR, et al. Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med. 1990;323(25):1729-1735.
7. Camisa C, Helm TN. Paraneoplastic pemphigus is a distinct neoplasia induced autoimmune disease. Arch Dermatol. 1993;129(7):883-886.
8. Poot AM, Diercks GF, Kramer D, et al. Laboratory diagnosis of paraneoplastic pemphigus. Br J Dermatol. 2013;169(5):1016-1024.
9. Svoboda SA, Huang S, Liu X, Hsu S, Motaparthi K. Paraneoplastic pemphigus: Revised diagnostic criteria based on literature analysis. J Cutan Pathol. 2021;48(9): 1133–1138.
