Thrombospondin Type-1 Domain containing 7A (THSD7A)

Immunology

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Description

Membranous glomerulonephritis ( MG ) is an autoimmune disease which typically presents with nephrotic syndrome or proteinuria. One-third of patients progress to end-stage renal disease ( 1 ). MG is more common in males than females ( 2:1 ) and has a peak incidence between 40 and 50 years of age. It is associated with autoantibodies against podocyte antigens present in the Bowman's capsule of the kidneys ( 2 ). The deposition of these antibodies leads to activation of complement at the podocyte surface, cell injury and urinary protein loss ( 2, 3 ). MG can be classified as either primary ( idiopathic ), which occurs in 75% of cases, or secondary. Secondary membranous is associated with malignancy, autoimmunity, infection and drugs. In 2009, the glomerular podocyte antigen phospholipase A2 receptor 1 ( PLA2R1 ) was identified as a major antigenic target in approximately 70% of primary MG cases ( 2, 4 ). Recently, antibodies to a second antigenic target, Thrombospondin type-1 domain-containing 7A ( THSD7A ), have been associated with the pathogenesis of primary MG ( 1, 2 ). TSHD7A is a 250-kD type I trans-membrane protein which is present in high concentrations within podocytes, specifically localised to podocyte endocytic compartments, foot processes and the slit diaphragm ( 1, 5 ). Anti-THSD7A antibodies are predominantly of the IgG4 subclass, although IgG1, IgG2 and IgG3 specific antibodies have been demonstrated in some primary MG patients ( 1 ). Recent studies have reported the presence of anti-THSD7A antibodies in 2.5 to 10 % of patients with primary MG, whom are seronegative for anti-PLA2R antibodies ( 1, 2, 3 ). Together, THSD7A- and PLA2R1-associated MG may now account for approximately 70 to 80% of cases, which further helps to distinguish primary from secondary MG ( 1, 2 ).

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Indications

Idiopathic Membranous glomerulonephritis.

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Sample Type

2mL Serum ( Gel 5mL Yellow tube ). Requests from outside Sheffield: Transport at ambient temperature via Royal Mail or Courier.

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Reference Range

Positive or Negative

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Turnaround Time

Within 2 weeks

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Testing Frequency

Weekly

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References

Tomas NM, Beck LH, Meyer-Schwesinger C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. New England Journal of Medicine. 2014; 371: 2277-2287. [Ref 1].
Larsen CP, Cossey LN and Beck LH. THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity. Modern Pathology. 2016; 29: 421-426. [Ref 2].
Ronco P, Debiec H. Pathophysiological advances in membranous nephropathy: time for a shift in patient's care. The Lancet. 2015; 385: 1983-1992. [Ref 3].
Beck LH, Bonegio RGB, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. New England Journal of Medicine. 2009; 361: 11-21. [Ref 4].
Godel M, Grahmmer F and Huber TB. Letter to the Editor: Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. New England Journal of Medicine. 2015; 372: 1073-1075. [Ref 5].

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See Also

PLA2R, Renal Biopsy

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