Titers are crucial for disease evaluation, therapy and risk assessment

Anti-PLA2R autoantibodies, moreover, provide important information about the clinical activity of the disease. Studies have shown that the course of disease and the success of therapy in patients with primary MN can be assessed by monitoring the anti-PLA2R antibody titer.

Hofstra and colleagues showed that a weak but statistically significant association exists between the anti-PLA2R titer and the clinical status of the disease as defined by proteinuria. They found that anti-PLA2R titers were high in patients with acute nephrotic syndrome (high proteinuria) but decreased or were absent in cases of spontaneous or treatment-induced remission (low proteinuria). If a relapse occurred, the antibody titer increased again. Based on the finding that spontaneous remissions occurred significantly less frequently in patients with initially highest antibody titers, they suggested that the antibody level also reflects the severity of primary MN.1,2

Modified from: Hofstra et al., CJASN 6, 1-5 (2011)
Serologischer Nachweis der Autoantikörper gegen PLA2R

Despite this close relationship, anti-PLA2R autoantibody titers as an immunological marker should still be discriminated from proteinuria, which is a clinical marker. Due to the hypothesized chronology in the pathogenesis of primary MN, it is assumed that the markers show similar but temporally shifted reactions during the course of disease.3

Modified from: Beck et al., Kidney Int 77, 765-770 (2010)
Modified from: Beck et al., Kidney Int 77, 765-770 (2010)

According to Beck et al., the decrease in antibody levels in monitored patients responsive to immunosuppressive therapy indeed preceded the decline in proteinuria by months.4 This was confirmed by a recent study, which indicated that the immediate immunological response in patients undergoing therapy also seems to be considerably stronger than the clinical response. Hoxha et al. found that immunosuppressive treatment of primary MN patients led to a reduction in anti-PLA2R titers of 81 % within three months, parallel to a 39% decline in proteinuria.5

Therefore, monitoring of anti-PLA2R titers can provide highly relevant indications of disease state and also of patients’ responsiveness to therapy. Moreover, the titer is more sensitive to changes in disease state than is proteinuria.

In a statistical analysis, Hoxha et al. additionally assessed the predictive value of anti-PLA2R. High titers were identified as an independent risk factor for not achieving a remission of proteinuria.5 Based on this, the antibody titer may influence a physician’s decision about the necessity and intensity of an immunosuppressive therapy of anti-PLA2R positive MN patients.

In a different approach aimed at defining the predictive value of anti-PLA2R, Seitz-Polski et al. intended to determine a possible association between the antibody titer and the risk of primary MN recurrence after kidney transplantation. A correlation between the anti-PLA2R titer at the time of transplantation and the risk of MN recurrence was not observed. A persistent presence of the autoantibodies within six months after organ transplantation, however, was strongly associated with MN relapse.6 This is consistent with a previous case report on a female patient, who experienced MN recurrence after kidney transplantation. Anti-PLA2R autoantibodies were detected in the patient before and three months after organ transplantation. After immunosuppressive therapy with Rituximab, the titer decreased to a tenth of its initial value preceding the declining proteinuria.7 Nevertheless, additional studies are needed to support the current concept of the predictive value of anti-PLA2R autoantibodies in assessing the risk of MN recurrence.

Modified from: Stahl et al., N Engl J Med (2010)
Modified from: Beck et al., Kidney Int 77, 765-770 (2010)

It is highly recommended to monitor anti-PLA2R titers in parallel to clinical markers such as proteinuria during medical treatment of primary MN patients.8 In addition to the antibody’s significance in disease diagnosis, the antibody titer can yield additional information on the status of disease and the direct immunological and clinical response to therapy.  Initial results suggest that anti-PLA2R titers further allow predictions on disease outcome, therapy requirements and the risk of recurrence after kidney transplantation.