The diagnostic performance of PLA2R and IgG subclass staining of kidney biopsies relative
to anti-PLA2R seropositivity in the differentiation of primary and secondary membranous
nephropathy (pMN, sMN) was examined. Besides PLA2R staining - which has a lower specificity
than anti-PLA2R antibody serology - there is insufficient knowledge to decide which
IgG1-4 subtype immunohistological patterns (IgG4-dominance, IgG4-dominance/IgG1-IgG4-codominance
or IgG4-dominance/IgG4-codominance with any IgG subtype) could be used to distinguish
between pMN and sMN.87 consecutive Hungarian patients (84 Caucasians, 3 Romas) with
the biopsy diagnosis of MN were classified clinically as pMN (n = 63) or sMN (n =
24). The PLA2R and IgG subclass staining was part of the diagnostic protocol. Anti-PLA2R
antibodies were determined by an indirect immunofluorescence test in 74 patients with
disease activity.For pMN, the sensitivity of anti-PLA2R seropositivity was 61.1%,
and the specificity was 90.0%; and similar values for PLA2R staining were 81.0%, and
66.7%, respectively. In all stages of pMN, IgG4-dominance was the dominant subclass
pattern, while the second most frequent was IgG3/IgG4-codominance. The sensitivity
and specificity scores were: IgG4-dominance 52.2% and 91.7%, IgG4-dominance/IgG3-IgG4-codominance
76.2% and 87.5%, IgG4-dominance/IgG1-IgG4-codominance 64.2% and 75%, and IgG4-dominance/codominance
with any IgG subclass 92.1% and 70.8%, respectively. Anti-PLA2R seropositivity, glomerular
PLA2R, and IgG4-dominance/codominance significantly correlated with each other. The
IgG4 subclass was rarely encountered in sMN.In our series, IgG4-dominance had the
highest specificity in the differentiation of MN, just as high as that for anti-PLA2R
seropositivity. The specificity values of PLA2R staining and IgG4-dominance/codominance
with any IgG subclass or IgG4-dominance/IgG1-IgG4 codominance were ≤ 75%. Apart from
IgG4 dominance, IgG4-dominance/IgG3-IgG4-codominance also had good statistical value
in differentiating pMN from sMN. As IgG subclass switching during the progression
of pMN was not the feature of our cohort, pMN in Hungarian patients is presumed to
be an IgG4-related disorder right from the start. Although anti-PLA2R seropositivity
has become the cornerstone for diagnosing pMN, if a kidney biopsy evaluation is conducted,
besides the staining of PLA2R antigen, the evaluation of IgG subclasses provides relevant
information for a differential diagnosis. Even in cases with IgG4-dominance, however,
malignancy should be thoroughly checked.
