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HelpEpic Code LAB12309891 Primary Membranous Nephropathy Diagnostic Cascade, Serum
Additional Codes
Mayo code: PMND1
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Useful For
Distinguishing primary from secondary membranous nephropathy using an algorithmic approach
Monitoring patients with membranous nephropathy at very low antibody titers
Screening for anti-phospholipase A2 receptor antibodies
Specimen Type
SerumSpecimen Required
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Centrifuge and aliquot serum into plastic vial within 2 hours of collection.
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 14 days | |
| Frozen | 14 days | ||
| Ambient | 8 hours |
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | OK |
| Gross icterus | OK |
Day(s) Performed
Monday, Wednesday, Friday
Reference Values
ANTI-PHOSPHOLIPASE A2 RECEPTOR (PLA2R) ENZYME-LINKED IMMUNOSORBENT ASSAY:
<14 RU/mL: Negative
14 to 19 RU/mL: Borderline
≥20 RU/mL: Positive
PLA2R IMMUNOFLUORESCENCE:
Negative
THROMBOSPONDIN TYPE-1 DOMAIN-CONTAINING 7A ANTIBODIES:
Negative
Clinical Information
Membranous nephropathy (MN) is a rare disease in which immune complexes deposit at the glomerular basement membrane, causing damage to the filtration barrier, resulting in proteinuria. Recent studies have shown that in approximately 70% of patients with primary MN (pMN), the immune complexes consist of autoantibodies against the podocyte protein M-type phospholipase A2 receptor (PLA2R).(1) There is also evidence that levels of anti-PLA2R autoantibodies correlate well with disease activity and progression.(2) The presence of anti-PLA2R antibodies could also potentially be used to differentiate pMN from other causes of nephrotic syndrome if a biopsy is not possible. Among patients with chronic kidney disease awaiting kidney transplantation, higher levels of anti-PLA2R could predict those more likely to recur after transplantation.(2)
Mayo Clinic Laboratory data suggest that there is a high-concordance between the enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay PLA2R results; however, the ELISA assay alone may be preferred for monitoring patients with membranous nephropathy over time for trends in anti-PLA2R antibody levels.
In the remaining 30% of patients with MN who are PLA2R-negative, anti-thrombospondin type-1 domain-containing 7A (THSD7A) was shown to have an approximate 10% prevalence (ie, about 3% of all primary MN patients).(3) Mouse podocytes express THSD7A and introduction of anti-THSD7A autoantibodies induces MN in murine models. Mouse podocytes do not express PLA2R so exogenous administration of anti-PLA2R does not recapitulate MN in mice.(4) Additionally, THSD7A has been described as a potential tumor antigen and, thus, it has been suggested that THSD7A-positive patients merit a thorough cancer screening.(5)
Cautions
This test should not be used as a stand-alone test but an adjunct to other clinical information. A diagnosis of primary or secondary membranous nephropathy (MN) should not be made on a single test result. The clinical symptoms, results on physical examination, and laboratory tests (eg, serological tests), when appropriate, should always be taken into account when considering the diagnosis of primary versus secondary MN.
Absence of circulating anti-phospholipase A2 receptor autoantibodies does not rule out a diagnosis of primary MN.
Interpretation
Therapy outcome can be monitored by measuring the anti-phospholipase A2 receptor (PLA2R) antibody titer. A titer increase, decrease, or disappearance generally precedes a change in clinical status. Thus, the determination of the antibody titer has a high predictive value with respect to clinical remission, relapse, or risk assessment after kidney transplantation.
According to the manufacturer's package insert, the EUROIMMUN Anti-PLA2R indirect immunofluorescence assay (IFA) was positive in 77.1% of patients with biopsy proven primary membranous nephropathy (pMN).(6) This corresponds well with published literature that approximately 70% of patients with pMN will have anti-PLA2R antibodies.
Reporting Name
Prim Membranous Nephropathy Diag, SMethod Name
EURO: Enzyme-Linked Immunosorbent Assay (ELISA)
PLA2I, THSD7: Indirect Immunofluorescence Assay (IFA)
Method Description
Enzyme-Linked Immunosorbent Assay:
The test kit provides microtiter strips, each with 8 break-off reagent wells. In the case of positive samples, specific IgG antibodies (also IgA and IgM) will bind to the antigens. To detect the bound antibodies, a second incubation is carried out using an enzyme-labelled antihuman IgG (enzyme conjugate) catalyzing a color reaction.(Package insert: Anti-PLA2R ELISA [IgG] Kit, EUROIMMUN US; V 07/08/2020)
Indirect Immunofluorescence Assay:
Diluted patient samples are incubated with combinations of substrates. If the reaction is positive, specific antibodies of classes IgA, IgG, and IgM attach to the antigens. In a second step, the attached antibodies are stained with fluorescein-labelled antihuman antibodies and made visible with a fluorescence microscope.(Package inserts: Anti-PLA2R IFA Kit, EUROIMMUN US; V 09/27/2018; Anti-THSD7A IIFT EUROPattern, EUROIMMUN US;V 06/11/2019)
CPT Code Information
83520
86255 (x1 or x2, if applicable)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| PMND1 | Prim Membranous Nephropathy Diag, S | 73737-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| EURO | Phospholipase A2 Receptor, ELISA, S | 73737-9 |
Report Available
3 to 7 daysTest Classification
See Individual Test IDsClinical Reference
1. Beck Lh Jr, Bonegio RGB, Lambeau G, et al: M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009 Jul 2;361(1):11-21
2. Schlumberger W, Hornig N, Lange S, et al: Differential diagnosis of membranous nephropathy with autoantibodies to phospholipase A2 receptor 1. Autoimmun Rev. 2014 Feb;13(2)108-113
3. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, et al: Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014 Dec 11;371(24):2277-2287. doi: 10.1056/NEJMoa1409354
4. Tomas NM, Hoxha E, Reinicke AT, et al: Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy. J Clin Invest. 2016 Jul 1;126(7):2519-2532. doi: 10.1172/JCI85265
5. Stahl PR, Hoxha E, Wiech T, Schroder C, Simon R, Stahl RAK: THSD7A expression in human cancer. Genes Chromosomes Cancer. 2017 Apr;56(4):314-327. doi: 10.1002/gcc.22440
6. Package insert: EUROIMMUN Anti-PLA2R IFA Kit, EUROIMMUN US; V 09/24/2018
Highlights
Anti-phospholipase A2 receptor (PLA2R) antibodies are highly specific for the diagnosis of primary membranous nephropathy.
As many as 70% to 75% of patients with primary membranous nephropathy are positive for anti-PLA2R.
A titer increase, decrease, or disappearance generally precedes a change in clinical status.
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| EURO | Phospholipase A2 Receptor, ELISA, S | Yes, (Order PLA2M) | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| PLA2I | PLA2R, Immunofluorescence, S | Yes | No |
| THSD7 | THSD7A Ab, S | Yes | No |
Forms
If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.