Lab Med Qual Assur.  2022 Mar;44(1):40-47. 10.15263/jlmqa.2022.44.1.40.

Cross-Reactivity of Disease-Specific Antibody Assays for the Detection of Current Infections: With Potentially Interfering Substances of Other Infections

• Gong DH
• Kim SH
• Kim HJ
• Lee A
• Han MS

• KMID: 2527804
• DOI: http://doi.org/10.15263/jlmqa.2022.44.1.40

Abstract

Background
Current infections are frequently diagnosed based on positive immunoglobulin (Ig) M results, although false positivity can occur. We evaluated cross-reactivity among infectious antibody (Ab) assays.
Methods
A total of 167 positive sera were collected for: rubella IgM and IgG, cytomegalovirus (CMV) IgM and IgG, Toxoplasma gondii (Toxo) IgG, human immunodeficiency virus (HIV) antigen (Ag)/Ab, hepatitis A virus (HAV) IgM and IgG, hepatitis C virus (HCV) Ab, herpes simplex virus (HSV) IgM and IgG, Epstein-Barr virus viral capsid Ag IgM, hepatitis B core (HBc) IgM, hepatitis B e Ab, and severe acute respiratory syndrome coronavirus 2 total Ab, Treponema pallidum IgM (each n=10) and Toxo IgM (n=7). All sera were tested with seven assays in duplicate: Architect rubella IgM, CMV IgM, Toxo IgM, HIV Ag/Ab, HAV IgM, anti-HCV (Abbott Laboratories, USA), and Elecsys HBc IgM (Roche Diagnostics GmbH, Germany). Additionally, sera showing repeatedly reactive were evaluated by following supplemental testing: Elecsys Toxo IgM, HIV Duo and HAV IgM, VIDAS rubella IgM and CMV IgM (bioMérieux SA, France); LIAISON XL CMV IgM (DiaSorin S.p.A., Italy); and HCV blot 3.0 (MP Diagnostics Inc., Philippines).
Results
Except Elecsys HBc IgM, six assays showed reactive for several sera, including other infectious Abs. Upon supplemental testing, Architect rubella IgM, CMV IgM, and anti-HCV showed reactive or gray zone for two sera with HSV IgM (κ=0.903), eight to fifteen with various Abs (κ=0.607–0.814), and one with HAV IgG (κ=0.960), respectively.
Conclusions
Architect rubella IgM, CMV IgM, and anti-HCV showed crossreactivity with reactive sera to other infectious Abs. Considering crossreactivity of Ab assays with other pre-existing infectious Abs, infectious Ab results should be carefully interpreted.

Keyword

Immunoassay; Viral antibodies; Immunoglobulin M; Immuno globulin G; Cross-reactivity