Test Catalog

Test Id : AFH

Factor H Autoantibody, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Detection and quantification of antibodies to factor H

 

Monitoring patients with known factor H autoantibodies

 

Aiding in the differential diagnosis of thrombotic microangiopathy and C3 glomerulopathies

Method Name
A short description of the method used to perform the test

Enzyme-Linked Immunosorbent Assay (ELISA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Factor H Autoantibody, S

Aliases
Lists additional common names for a test, as an aid in searching

Antibody Factor H

Anti-CFH Antibody

Anti-Complement Factor H

CFH Autoantibody

Specimen Type
Describes the specimen type validated for testing

Serum Red

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Collection Instructions:

1. Immediately after specimen collection, place the tube on wet ice.

2. Centrifuge and aliquot serum into plastic vial.

3. Freeze specimen within 30 minutes.

Additional Information: If the specimen is to be shared with AHUSD / Atypical Hemolytic Uremic Syndrome Complement Panel, Serum and Plasma, only serum collected in a red-top tube is acceptable.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.4 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Red Frozen (preferred) 28 days
Refrigerated 28 days
Ambient 14 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Detection and quantification of antibodies to factor H

 

Monitoring patients with known factor H autoantibodies

 

Aiding in the differential diagnosis of thrombotic microangiopathy and C3 glomerulopathies

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Complement factor H (FH) is an important regulator of cell-bound activated C3b, and most importantly of activated C3b in the fluid phase. It is estimated that C3 activation takes place at a rate of 1% to 2%, thus constant activity of FH and other regulators is essential to retain control of complement’s alternative pathway. Anti-factor H (AFH) is an autoantibody that interferes with the ability of FH to bind the C3 convertase, therefore allowing unrestricted amplification of C3b in the complement cascade.

 

AFH is predominantly seen in children between the ages of 9 and 13 years but can also affect adults. AFH is found in atypical hemolytic uremic syndrome (AHUS) and in C3 glomerulopathies. AHUS is a form of thrombotic microangiopathy (TMA), a condition that can cause small blood vessels in the kidneys to become damaged and inflamed as a result of clots forming in the vessels. The clots clog the glomeruli of the kidneys and can cause problems with the kidney' s ability to filter and eliminate waste products. Compared to typical HUS, which is caused by Shiga toxin-producing bacterial infection, aHUS is a diagnosis of exclusion, associated with genetic variants in the complement alternative pathway or acquired autoantibodies that contribute to uncontrolled activation of the complement system. C3 glomerulopathies (C3G) are rare kidney diseases resulting from complement deposition in the kidney (mostly C3 fragments) and causing glomerular damage. C3G may have autoimmune or genetic causes and is attributed mostly to dysfunction of the complement alternative pathway.

 

AFH are found in 6% to 10% of aHUS patients, and the presence or absence of AFH can be a determinant of whether immunosuppressive therapy is warranted versus complement-blocking therapy.(1) Deletion of the CFHR1 gene, with or without other CFHR genes, can result in predisposition to generation of AFH; however, not all individuals with CFHR1 deletion develop AFH, and conversely, some individuals with the autoantibody do not have a CFHR1 deletion.(2) Most commonly, the deletion encompasses both the CFHR1 and CFHR3 genes. The allele frequency of the CFHR3/CFHR1 deletion varies among populations, from 0% in Japanese and South American populations to 54.7% in Nigeria; similarly, the frequency of homozygosity for the deletion ranges from 0% up to 33% in Nigeria.(3) Interestingly, while AFH are much more common in aHUS cohorts from India, accounting for approximately 50% of cases, the population frequency of homozygous CFHR1 deletion is 9.5%, which is not significantly higher than in other populations.(4,5) The mechanism that results in AFH formation in the presence of the deletion remains unknown. Most of the autoantibodies inhibit FH function by binding and blocking the C-terminus, impairing its ability to bind endothelial cell surfaces, sialic acids, and C3b; however, in some individuals, the AFH may recognize other regions, such as the N-terminal SCR1-4.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

<15.8 U/mL

Interpretation
Provides information to assist in interpretation of the test results

Absent (<15.8 U/mL): Antibodies to factor H are not detected.

 

Present (> or =15.8 U/mL): Antibodies to factor H are detected. Clinical correlation recommended.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Healthy individuals may see false-positive results for anti-factor H (AFH) since the diseases where AFH is pathogenic are so rare.

 

Positive AFH results can occur in healthy individuals and in IgA nephropathy. AFH could be an incidental finding in patients with diseases other than atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G). This is most likely due to the multifactorial nature of the diseases and differences in penetrance for genetic variants.

 

Results should be interpreted in the context of other complement assays and other laboratory tests in the evaluation of thrombotic microangiopathies or C3G.

 

Use of caution is suggested on a finding of AFH in the clinical setting.

 

This assay to measure AFH is not standardized to European methods and results obtained by other laboratories can only be compared qualitatively.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Ekdahl KN, Persson B, Mohlin C, Sandholm K, Skattum L, Nilsson B: Interpretation of serological complement biomarkers in disease. Front Immunol. 2018 Oct 24;9:2237. doi: 10.3389/fimmu.2018.02237

2. Jozsi M, Licht C, Strobel S, et al: Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood. 2008 Feb 1;111(3):1512-1514. doi: 10.1182/blood-2007-09-109876

3. Holmes LV, Strain L, Staniforth SJ, et al: Determining the population frequency of the CFHR3/CFHR1 deletion at 1q32. PLoS One. 2013 Apr 16;8(4):e60352. doi: 10.1371/journal.pone.0060352

4. Sinha A, Gulati A, Saini S, et al: Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int. 2014 May;85(5):1151-1160. doi: 10.1038/ki.2013.373

5. Durey MA, Sinha A, Togarsimalemath SK, Bagga A: Anti-complement-factor H-associated glomerulopathies. Nat Rev Nephrol. 2016 Sep;12(9):563-578. doi: 10.1038/nrneph.2016.99

6. Blanc C, Togarsimalemath SK, Chauvet S, et al: Anti-factor H autoantibodies in C3 glomerulopathies and in atypical hemolytic uremic syndrome: one target, two diseases. J Immunol. 2015 Jun 1;194(11):5129-5138. doi: 10.4049/jimmunol.1402770

7. Zhang Y, Ghiringhelli Borsa N, Shao D, et al: Factor H autoantibodies and complement-mediated diseases. Front Immunol. 2020 Dec 15;11:607211. doi: 10.3389/fimmu.2020.607211

8. Sanchez-Corral P, Pouw RB, Lopez-Trascasa M, Jozsi M: Self-damage caused by dysregulation of the complement alternative pathway: Relevance of the factor H protein family. Front Immunol. 2018 Jul 12;9:1607. doi: 10.3389/fimmu.2018.01607

9. Dragon-Durey MA, Blanc C, Roumenina LT, et al: Anti-factor H autoantibodies assay. Methods Mol Biol. 2014;1100:249-56. doi: 10.1007/978-1-62703-724-2_20

Method Description
Describes how the test is performed and provides a method-specific reference

The anti-factor H enzyme-linked immunoassay assay for the quantitation of antibodies to complement factor H is a 3-step procedure. In the first step, standards, controls, and diluted patient specimens are incubated with human recombinant complement factor H immobilized on a microwell plate. During this incubation, antibodies to factor H (AFH) present in the standards, controls, and patient sample will bind to the factor H-coated microwell plate. After incubation, a wash cycle removes the unbound material. In the second step, anti-human IgG conjugated to horseradish peroxidase (HRP) is added to the wells and incubated. The conjugate reacts with the AFH bound to the microwell plate. After incubation, a wash cycle removes the excess conjugate. In the third step, a chromogenic enzyme substrate is added to the wells and incubated. The bound HRP-conjugate reacts with the substrate forming a blue color. The enzyme reaction is stopped by dispensing an acidic solution into the wells, changing the color of the solution from blue to yellow. The color intensity of the reaction mixture is measured spectrophotometrically at 450 nm and is directly proportional to the amount of AFH present in the patient specimens, standards, and controls.(Package insert: Anti-Faktor H. GA Generic Assays GmbH; 11/2015)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 8 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83520

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
AFH Factor H Autoantibody, S In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
AFH Factor H Autoantibody, S In Process

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports