Test Catalog

Test Id : MBLF

Mannan Binding Lectin Complement Pathway, Functional, Serum

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

Investigating recurrent meningococcal disease in young children

 

Investigating recurrent or severe infections in adults

 

Investigating glomerular kidney diseases

 

Additionally, deficiencies or dysregulation within the complement system may be identified in patients when this test is used in combination with related tests.

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

MBL Complement Path, Func, S

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

MBL

Lectin Pathway

Mannose Binding Lectin

Mannan Binding Lectin

Functional Complement

Specimen Type
Describes the specimen type validated for testing

Serum Red

Ordering Guidance

The most appropriate primary assays to use as screening methods for complement deficiencies are COM / Complement, Total, Serum and AH50 / Alternative Complement Pathway, Functional, Serum. Abnormal results in one or the other, none, or both assays will help direct further testing. If total complement and AH50 are both normal but the suspicion of a complement deficiency remains, this test for the lectin pathway function is recommended. After the initial 3 pathways of complement functional status are evaluated, the analysis of individual components and regulators may uncover functional or quantitative defects in certain components.

 

This test is rarely useful when ordered in isolation.

 

As the heat-labile fraction of the immune system, complement activation in vitro has been a challenge for researchers and scientists. Because of the thermal instability of complement proteins, it is often necessary to repeat testing to rule out a possible pre-analytical issue with a sample type, real complement consumption, or dysregulation.

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

Patient Preparation:

1. If plasma exchange has been performed, wait 48 hours before collecting the specimen.

2. Fasting is preferred.

Collection Container/Tube: Red top (serum gel/SST are not acceptable)

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

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

2. Centrifuge at 4 degrees C and aliquot serum into plastic vial.

3. Freeze specimen within 30 minutes.

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) 14 days

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

Investigating recurrent meningococcal disease in young children

 

Investigating recurrent or severe infections in adults

 

Investigating glomerular kidney diseases

 

Additionally, deficiencies or dysregulation within the complement system may be identified in patients when this test is used in combination with related tests.

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

Complement proteins are components of the innate immune system. There are 3 pathways to complement activation:  the classical pathway, the alternative (or properdin) pathway, and the lectin (or mannan binding lectin: MBL) pathway.

 

The total complement (CH50) assay (COM / Complement, Total, Serum) is the best screening assay for complement abnormalities of the classical complement pathway (C1qrs, C4, C2, C3, C5, C6, C7, C8, C9). The COM 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.

 

Abnormalities in the alternative pathway may be evaluated with the AH50 functional assay (AH50 / Alternative Complement Pathway, Functional, Serum). The alternative pathway shares C3 and C5 through C9 components but has unique early complement components designated factors D, B, and P, as well as regulatory factors H and I. This pathway can be activated by hydrolysis of C3 or by microbial polysaccharides and does not require immune complex formation as a trigger. Patients with deficiencies in the alternative pathway factors (D, B, P, H, and I) or late complement components (C3, C5-C9) are unusually susceptible to recurrent Neisserial meningitis. Dysregulation of the alternative pathway is also observed in cases of atypical hemolytic uremic syndrome and rare kidney diseases such as C3 glomerulopathies.(1)

 

MBL is an acute phase protein, one of several lectins and collectins that initiate lectin pathway complement activity. These proteins play a role in host defense, recognizing pathogen- and damage-associated molecular patterns. MBL associates with MBL-associated serine proteases (MASP-1, -2, and -3) to activate complement components C2 through C9. MBL deficiency is a common finding worldwide due to the broad genetic distribution of deficient MBL2 alleles (5%-30% or higher in isolated populations).(1-3) Seven haplotypes are commonly observed, with a potential for 28 possible combinations.(4)

 

MBL activity of less than 10% may be found in a normal population at frequencies of 20% to 30%, a finding confirmed by Mayo Clinic during validation studies.

 

MBL function assessment is recommended as second-tier testing when CH50 and AH50 are both within reference intervals, and the clinical presentation of recurrent infections, along with suspicion of complement dysregulation, remains in the differential.

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.

> or =10%

Interpretation
Provides information to assist in interpretation of the test results

Low (<10%) mannan-binding lectin (MBL) pathway activity is consistent with very low or absent MBL protein in the context of normal alternative pathway (AH50) and normal classical pathway (CH50) activity. Not all individuals with decreased MBL function will manifest with clinical symptoms. MBL pathway function test results must be interpreted with clinical presentation, other comorbidities (autoimmune disease, infection, malignancy), and the overall status of the immune system (primary and secondary immunodeficiencies). In addition, identification of an MBL deficiency does not exclude other etiologies that would predispose individuals to an increased risk of infection.

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

This assay is a functional test and is dependent on correct sampling, storage, and shipping conditions. Both degradation by temperature and consumption of complement components will lead to falsely low function results. These are difficult to differentiate from real complement dysregulation.

 

While preanalytic handling can lead to falsely low results, it is far less likely that it would lead to falsely normal results.

 

Complement testing may be ordered in several circumstances where standard treatment includes plasmapheresis or plasma exchange. The procedure itself, if traumatic, may activate complement so may not reflect what is going on with the patient's complement system. In addition, the plasma exchange may include donor complement proteins. The recommendation is to collect blood prior to the plasma exchange whenever possible.

 

Functional results inconsistent with the clinical history should be verified with a new blood draw.

 

Specimens should be frozen immediately after collection.

 

The use of complement C5 inhibitor therapies such as eculizumab and ravulizumab will result in the blocking of C5. C5 is necessary for the complement function to progress until the formation of the membrane attack complex. Hence, in the presence of eculizumab or ravulizumab, results for CH50, AH50, or MBLF will be decreased or undetectable.

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

1. Willrich MAV, Braun KMP, Moyer AM, Jeffrey DH, Frazer-Abel A. Complement testing in the clinical laboratory. Crit Rev Clin Lab Sci. 2021 Nov;58(7):447-478. doi: 10.1080/10408363.2021.1907297

2. Heitzeneder S, Seidel M, Forster-Waldl E, Heitger A. Mannan-binding lectin deficiency - Good news, bad news, doesn't matter? Clin Immunol. 2012 Apr;143(1):22-38. doi: 10.1016/j.clim.2011.11.002

3. Kalia N, Singh J, Kaur M. The ambiguous role of mannose-binding lectin (MBL) in human immunity. Open Med (Wars). 2021 Feb;16(1):299-310. doi: 10.1515/med-2021-0239

4. Eisen DP, Osthoff M. If there is an evolutionary selection pressure for the high frequency of MBL2 polymorphisms, what is it? Clin Exp Immunol. May 2014;176(2):165-71. doi: 10.1111/cei.12241

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

The Wieslab enzyme-linked immunosorbent assay complement assay for the mannan-binding lectin (MBL) pathway combines principles of the hemolytic assay for complement activation with the use of labeled antibodies specific for neoantigens produced as a result of complement activation. The micro titer plate strips are coated with mannan. Patient serum is diluted in diluent containing specific blocker to ensure that only the MBL pathway is activated. During the first incubation, the diluted patient serum in the wells is activated by the coating. The wells are then washed and C5b-9 membrane attack complex (MAC) is detected with a specific alkaline phosphatase labeled antibody to the neoantigen expressed during MAC formation. After a final wash, an alkaline phosphatase substrate is added. The amount of MBL pathway complement activity correlates with the color intensity of the solution and is measured by absorbance (optical density).(Mollnes TE, Jokiranta TS, Truedsson L, et al: Complement analysis in the 21st century. Mol Immunol. 2007;44[16]:3838-49; Willrich MAV, Braun KMP, Moyer AM, Jeffrey DH, Frazer-Abel A. Complement testing in the clinical laboratory. Crit Rev Clin Lab Sci. 2021:1-51)

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.

Wednesday

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.

86161

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
MBLF MBL Complement Path, Func, S 74522-4
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.
MBLF MBL Complement Path, Func, S 74522-4

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