Combined aHUS Lab Diagnostics

Combined aHUS Lab Diagnostics

 

We have established a combined aHUS lab diagnostics service in Newcastle upon Tyne Hospitals that encompasses genetic and immunological evaluation of the complement system (and ADAMTS13 activity) to facilitate diagnosis of aHUS and exclusion of secondary causes of TMA (including TTP).

 

Tests Performed at Combined aHUS Lab Diagnostics

Serological testing

  • C3, C4, CH100, AH100, FH, FI, FB, sC5b-9
  • FH autoantibodies

Whole Blood Testing

  • CD46 expression on neutrophils

Genetic testing

  • Coding exons of CFH, CFI, CD46, C3, CFB, DGKE and MMACHC
  • Copy number of CFH, CFI, CD46, CFHR1, CFHR3
  • C5 Eculizumab non responder SNPs (p.R885H; p.R885C)

Screening for Inherited and Acquired Complement Abnormalities

Screening for inherited and acquired complement abnormalities is recommended in all patients with a potential diagnosis of aHUS. We recommend screening for the following complement abnormalities that have all been described in aHUS:

  • mutation screening of CFH, CFI, CD46, C3 and CFB

  • copy number of CFH, CFI, CD46, CFHR3 and CFHR1

  • screening for factor H autoantibodies

The single nucleotide polymorphisms (SNPs) in C5 (p.R885H; p.R885C) that predicts Eculizumab non-response is routinely screened.

Screening for Non-Complement Abnormalities

Genetic screening is routinely performed for DGKE and MMACHC as they predict Eculizumab non response and guide alternative therapies.

Rare familial cases of Eculizumab non responsive TMAs have been described with INF2 mutations and screening can be performed on request.

Controversy exists as to the role of THBD in aHUS and screening can be performed on request.

Measurement of ADAMTS13 Activity

We recommend that a plasma sample is sent for the measurement of ADAMTS13 activity as soon as possible AND prior to the patient receiving plasma products to exclude a diagnosis of TTP in patients with an acute TMA. Assays for ADAMTS13 activity are also available locally in some Trusts.

We offer measurement of ADAMTS13 levels as part of our combined aHUS lab diagnostics service at NRCTC. This can be done following EMERGENCY REFERRAL in patients being considered for eculizumab. Please see our combined aHUS lab diagnostics service request form for information regarding handling and shipping. An ADAMTS13 activity of greater than 10% excludes TTP.

When to Use Our Service

The above tests can be performed at the combined aHUS lab diagnostics in patients with a potential diagnosis of aHUS and in patients commenced on eculizumab.

Samples should be collected and sent to the combined aHUS lab diagnostics service in Newcastle upon Tyne Hospitals following discussion with the consultant nephrologist on-call at the National aHUS service via the EMERGENCY REFERRAL pathway.

In patients with a potential diagnosis of aHUS

We will screen for known complement and non-complement abnormalities that associate with aHUS. We will measure C3, C4, FB, sC5b-9 and also serum FH and FI levels and CD46 expression on neutrophils as evidence of low levels of complement regulators, interpreted in conjunction with mutation screening of CFH, CFI and CD46.

In patients with aHUS on eculizumab

Testing for evidence of complement blockade is recommended during follow-up whilst the patient is receiving eculizumab. Appropraite tests should be sent for monitoring of complement blockade once patients are stable on eculizumab. Additional samples may be required and will be discussed with the referring consultant on a case-by-case basis.

We can test for by CH100 and AH100 in our lab. Please discuss with us if you require these tests.

How to send us samples

Full instructions for sampling and transporting to the combined aHUS lab diagnostic services at in Newcastle upon Tyne Hospitals are on the request form.

ALL tests are paid for by NHS England as part of the diagnostic and follow-up pathways in patients referred to the national aHUS service for consideration of eculizumab.