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HelpTest ID: AH50 Alternative Complement Pathway, Functional, Serum
Reporting Name
Alternative Complement Path Func, SUseful For
Investigation of suspected complement dysregulation in the alternative pathway, atypical hemolytic uremic syndrome, C3 glomerulonephritis, and dense-deposit disease
Specimen Type
SerumOrdering Guidance
This test and COM / Complement, Total, Serum are the most appropriate primary assays to use as screening methods for complement deficiencies. Abnormal results in one or the other, neither or both assays will help direct further testing.
This test is rarely useful when ordered in isolation.
Specimen Required
Patient Preparation:
1. Fasting: 8 hours, preferred but not required
2. Do not collect a specimen for at least 48 hours following plasma exchange.
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 Serum
Collection Instructions:
1. Immediately after specimen collection, place the tube on wet ice and allow specimen to clot.
2. Centrifuge at 4° C and aliquot serum into a plastic vial.
3. Within 30 minutes of centrifugation, freeze specimen. Specimen must be placed on dry ice if not frozen immediately.
Note: If a refrigerated centrifuge is not available, it is acceptable to use a room temperature centrifuge, provided the specimen is kept on ice before centrifugation, and immediately afterward, the serum aliquoted and frozen.
Specimen Minimum Volume
Serum: 0.75 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Frozen | 14 days |
Reference Values
≥46% normal
Day(s) Performed
Varies
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
86161
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| AH50 | Alternative Complement Path Func, S | 74520-8 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 88676 | Alternative Complement Path Func, S | 74520-8 |
Clinical Information
Complement proteins are components of the innate immune system. There are 3 pathways to complement activation:
1. The classical pathway
2. The alternative (or properdin) pathway
3. The lectin (or mannose-binding lectin, MBL) pathway
The total complement (CH50) assay (COM / Complement, Total, Serum) assesses the classical complement pathway including early components that activate the pathway in response to immune complexes (C1q, C2 and C4), as well as the terminal complement components (C3, C5, C6, C7, C8, C9) involved in the formation of the membrane attack complex (MAC). The CH50 assay will be abnormal if there are specific hereditary or acquired C1-C9 complement component deficiencies or if there is consumption of complement due to immune (or autoimmune) complexes.
This assay is a screening test for complement abnormalities in the alternative pathway. The alternative complement (AH50) pathway shares C3 and C5-C9 components but has unique early complement components designated factors D, B, and properdin, as well as control proteins factor H and factor I. This pathway can be activated by spontaneous hydrolysis of C3 or by microbial polysaccharides and does not require immune complex formation. Patients with disseminated infections with pyogenic bacteria in the presence of a normal CH50 may have a decreased AH50 due to hereditary or acquired deficiencies of the alternative pathway. Patients with deficiencies in the alternative pathway factors (D, B, properdin, H, and I) or late complement components (C3, C5-C9) are highly susceptible to recurrent Neisserial meningitis. The combined use of the CH50 and AH50 assays allows identification of the specific pathway abnormality.
This test can also be used to monitor complement blockade by therapies targeting the complement pathways, primarily the C5 inhibitors.
Interpretation
Absent complement alternative pathway (AH50) in the presence of a normal total hemolytic complement (CH50) suggests an alternative pathway component deficiency.
Normal AH50 with absent CH50 suggests an early (C1, C2, C4) classic pathway deficiency.
Absent AH50 and CH50 suggests a late (C3, C5, C6, C7, C8, C9) component deficiency or complement consumption.
Absent AH50 and CH50 in the presence of a normal C3 and C4 suggests a late (C5, C6, C7, C8, C9) component deficiency.
Normal CH50 and AH50 in the presence of recurrent infection and continued suspicion of complement deficiency, suggest testing for lectin pathway function.
Clinical Reference
1. Frank MM. Medical intelligence current concepts: complement in the pathophysiology of human disease. N Engl J Med. 1987;316(24):1525-1530. doi:10.1056/NEJM198706113162407
2. Thurman JM, Holers VM. Brief reviews: the central role of the alternative complement pathway in human disease. J Immunol. 2006;176(3):1305-1310. doi:10.4049/jimmunol.176.3.1305
3. Frank MM. Complement deficiencies. Pediatr Clin North Am. 2000;47(6):1339-1354. doi:10.1016/s0031-3955(05)70274-1
4. Go RS, Winters JL, Leung N, et al. Thrombotic microangiopathy care pathway: A consensus statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group. Mayo Clin Proc. 2016;91(9):1189-1211. doi:10.1016/j.mayocp.2016.05.015
5. Willrich MAV, Andreguetto BD, Sridharan M, et al. The impact of eculizumab on routine complement assays. J Immunol Methods. 2018;460:63-71. doi:10.1016/j.jim.2018.06.010
Report Available
3 to 5 daysMethod Name
Enzyme-Linked Immunosorbent Assay (ELISA)
Forms
If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.
mcl-tma