Rheumatoid Arthritis Profiles

Diagnosis and classification of rheumatoid arthritis (RA) have relied heavily on the presence of Rheumatoid Factor (RF) and Anti-CCP (Cyclic Citrullinated Peptide). However, 20–25% of patients with RA (and up to 50% of those with suspected early RA) may be seronegative for both RF and Anti-CCP.1 Novel markers may be useful in identifying more early RA patients, stratifying patients at risk of joint destruction and monitoring disease activity and treatment response.

  • Most comprehensive diagnostic and prognostic profile for RA. Along with RF and Anti-CCP Ab, it includes four novel markers (14-3-3 eta, Anti-CEP-1, Anti-Sa, and Anti-CarP) that enhance the ability to diagnose early or established RA as well as to predict disease severity


    Rheumatoid Factor (RF) by Turbidimetry , Anti-CCP (Cyclic Citrullinated Peptide) Ab, IgG & IgA, 14-3-3 eta, Anti- CEP1 (citrullinated alpha-enolase 1) Ab, Anti-Sa (citrullinated vimentin) Ab, Anti-CarP (carbamylated protein) Ab

  • Novel reflexive profile for RA that if negative for traditional markers, RF and Anti-CCP, reflexes to four novel markers (14-3-3 eta, Anti-CEP1, Anti-Sa, Anti-CarP) that comprise SeroNeg RAdx4 which is designed to enhance diagnosis of RA and early RA as well as predict disease severity


    RA Profile (Rheumatoid Factor and Anti-CCP) with Reflex to SeroNeg RAdx4 (14-3-3 eta, Anti-CEP1, Anti-Sa, Anti-CarP

  • Diagnostic profile for Seronegative patients (who have tested RF-negative and Anti-CCP- negative) designed to enhance the diagnosis of RA and early RA. It is comprised of four novel markers (14-3-3 eta, Anti-CEP1, Anti-Sa, Anti-CarP) that may also predict RA disease severity


    14-3-3 eta protein; Anti-CEP1 (citrullinated alpha-enolase 1) Ab; Anti-Sa (citrullinated vimentin) Ab; Anti-CarP (carbamylated protein) Ab

  • Profile for Rheumatoid Arthritis that may increase the specificity and predictive value of RF by Turbimetry (a separate test) when all three RF isotypes are detected. This profile may also help predict joint damage


    RF IgG, IgA and IgM isotypes are determined by individual enzyme immunoassays

ANA Profiles and Related Tests

Anti-nuclear antibody (ANA) by indirect immunofluorescence assay (IFA) is the gold standard screening test that detects autoantibodies to the nuclear components of HEp-2 cells.2 A positive ANA by IFA is reported as titer and pattern. However, IFA patterns are not always specific. Profiles comprised of monospecific assays for individual autoantibodies have diagnostic and potential prognostic utility for several autoimmune diseases.

  • Comprehensive diagnostic profile deliberately curated to aid in the differential diagnosis of eight autoimmune disease states: systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), Sjögren's syndrome, limited scleroderma, diffuse scleroderma, drug-induced lupus and autoimmune thyroid disease

    This profile includes unique reflexing strategies designed to detect more true positives and Anti-double stranded DNA by Farr radioimmunoassay which has very high specificity for SLE and is reported as a numeric result with reference range of <8.0 IU/m


    ANA by IFA is performed and reported with titer and pattern. A lower cutoff 1:40 increases the diagnostic sensitivity

    This profile is reflexive; if ANA is positive, the following 14 components are performed:

    • Anti-dsDNA Ab by Farr, Anti-Sm, C3 Complement; C4 Complement, Anti-Cardiolipin Ab (IgG, IgA & IgM Isotypes), Anti-U1 RNP, Anti-Ro (SS-A) Ab,Anti-La (SS-B) Ab,RF by Turbimetry, Anti-CCP (Cyclic Citrullinated Peptide) Ab, Anti-Centromere Ab, Anti-Scl-70 Ab, Anti-Chromatin Ab , Anti-TPO (Thyroid Microsomal Peroxidase) Ab
    • If ANA is negative, an Anti-Ro (SS-A) Ab is performed to catch the small percentage of false negative ANA by IFA. If Anti-Ro is positive, then all profile components are performed

    Anti-Scl70 positivity by ELISA is confirmed using a second method to improve its predictive value in identifying diffuse scleroderma

  • Unique screening profile with the novel Anti-DFS70 designed to triage ANA-positive patients by identifying those most likely to benefit from a rheumatology specialist. Positive Anti- DFS70 in the absence of the other autoantibodies confers a likelihood ratio of 10.9 for the absence of systemic autoimmune rheumatic disease (SARD)


    Anti-DFS70 Ab, Anti-Sm Ab, Anti-U1 RNP Ab, Anti-Ro (SS-A) Ab, Anti-La (SS-B) Ab, Anti-Scl70 Ab, Anti-Jo1 Ab

  • Anti-DFS70 antibodies may help identify individuals who do not have an ANA-associated autoimmune rheumatic disease (AARD) especially in the absence of significant clinical findings.3 Anti-DFS70 Ab, especially when positive in isolation (i.e. in the absence of AARD-associated autoantibodies), may prevent unnecessary referrals and examinations of ANA-positive individuals4

  • Do All is not reflexive; it is a separate test code; all components of ANA 12 Plus are always performed and reported

  • Disease monitoring profile designed to aid in the assessment of renal disease associated with SLE


    Anti-dsDNA Ab by Farr, Anti-C1Q Ab, C3 Complement, C4 Complement

Myositis Profiles and Related Tests

Inflammatory myopathies (or idiopathic inflammatory myopathies), commonly known as myositis, including dermatomyositis, polymyositis, anti-synthetase syndrome and overlap myositis, are systemic diseases that affect multiple organs and can cause severe impairment.

  • Most comprehensive diagnostic myositis profile designed to cast the widest net for autoantibodies indicative of dermatomyositis (DM), polymyositis (PM), and anti-synthetase syndrome as well as other diseases that overlap with idiopathic inflammatory myopathies (IIM)

    This unique profile featuring gold standard RIPA gel radiography aids not only in differential diagnosis but also in characterization of disease pattern, severity and other risks


    Anti-Jo-1 Ab, Anti-PL-7 Ab, Anti-PL-12 Ab, Anti-EJ Ab, Anti-OJ Ab, Anti-MDA5 Ab (CADM-140), Anti-NXP-2 Ab, Anti-TIF-1γ Ab, Anti-SAE1 Ab, Anti-Mi-2 Ab, Anti-SRP Ab, Anti-SS-A 52kD Ab, Anti-Ku Ab, Anti-U1 RNP Ab, Anti-U2 RNP Ab, Anti-U3 RNP (Fibrillarin Ab), Anti-PM/Scl-100 Ab

     

  • Marker specific for a distinct form of myositis, sporadic inclusion body myositis (sIBM)

  • Marker associated with and specific for necrotizing myopathy most often caused by exposure to statin drugs

MyoMarker® 3 Plus employs RIPA gel radiography. This complex method utilizes immunoprecipitation, gel electrophoresis (SDS-PAGE) and autoradiography to identify radioisotope-labelled proteins from human erythroleukemic cell extracts that are targeted by autoantibodies in patient serum. RIPA gel radiography is a powerful, reliable technology that has been used and refined over more than 30 years to identify many PM/DM autoantibodies with high sensitivity, specificity and reproducibility. It is the original methodology of studies that defined various myositis-specific and myositis-associated antibodies.7

Scleroderma Profile and Related Tests

Scleroderma or systemic sclerosis is a systemic autoimmune rheumatic disease (SARD) characterized by hardening of the skin and other organs. Testing is centered on diagnosis and differentiation between limited (also known as CREST syndrome with calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia) and diffuse forms.

  • Most comprehensive scleroderma profile designed to facilitate early diagnosis and intervention as well as differentiation between limited and diffuse forms of scleroderma


    Anti-Nuclear Ab (ANA) by IFA, Anti-Centromere Ab, Anti-Th/To Ab, Anti-U1 RNP Ab, Anti-U3 RNP (Fibrillarin) Ab, Anti-RNA Polymerase III Ab, Anti-Scl 70 Ab, Anti-PM/Scl-75 Ab, Anti-PM/ Scl-100 Ab

  • Important marker for scleroderma, incorporating a unique second method that improves positive predictive value

Interstitial Lung Disease Profiles

Interstitial lung disease (ILD) is a frequent manifestation and cause of morbidity and mortality in systemic autoimmune rheumatic diseases (SARD) including systemic sclerosis (SS), Sjögren's syndrome (SjS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM) and ANCA-associated vasculitis (AAV). Early detection and diagnosis of ILD and its underlying SARD may offer the opportunity to target management and improve clinical course by suppressing lung inflammation, restricting fibrotic response and limiting irreversible tissue damage.5

  • Unique, comprehensive profile to diagnose underlying autoimmune diseases that can cause ILD and to identify rheumatic patients at risk for rapidly progressive ILD


    Anti-Scl-70 Ab, Anti-PM/Scl-100 Ab, Anti-Jo-1 Ab, Anti-EJ Ab, Anti-OJ Ab , Anti-PL-7 Ab, Anti-PL-12 Ab, Anti-MDA5 Ab, Anti-SRP Ab. Anti-Ku Ab, Anti-SSA 52 kD Ab

    ANA by IFA, If positive, reflexes to Anti-dsDNA by Farr, Anti-Sm Ab, Anti-U1 RNP Ab, Anti-La (SS-B) Ab, Anti-Ro (SS-A) Ab

    ANCA by IFA, if positive, reflexes to Anti-MPO Ab and Anti-PR3 Ab, RF by Turbimetry, Anti-CCP Ab

  • Profile to identify myositis patients at risk for ILD


    Anti-PM/Scl-100 Ab, Anti-Jo-1 Ab, Anti-EJ Ab, Anti-OJ Ab, Anti-PL-7 Ab, Anti-PL-12 Ab, Anti-MDA5 Ab, Anti-SRP Ab, Anti-Ku Ab, Anti-SSA 52 kD Ab

MyoMarker® 3 Plus, Scleroderma Comp Plus, ILDdx and Interstitial Lung Profiles employ RIPA gel radiography. RIPA gel radiography is a powerful, reliable technology that has been used and refined for more than 30 years to identify many PM/DM autoantibodies with high sensitivity, specificity and reproducibility. It is the original methodology of studies that defined various myositis-specific and myositis-associated antibodies.7

Sjögrenʼs Profile and Related Test

Sjögrenʼs syndrome is a systemic autoimmune rheumatic disease (SARD) characterized by dry eyes, dry mouth and fatigue and can involve multiple organs such as the kidneys, gastrointestinal system, blood vessels, lungs, liver, pancreas and the central nervous system.

  • Unique Sjögrenʼs profile with Anti-Fodrin Abs to improve early diagnosis


    Anti-Ro (SS-A) Ab; Anti-La (SS-B) Ab; Anti-Fodrin Abs, IgG and IgA

  • Unique markers that may improve the ability to diagnose early stage Sjögrenʼs

ANCA Profile and Other Related Tests

Other autoimmune diseases like ANCA-associated vasculitides (AAV), inflammatory bowel disease (IBD) and autoimmune liver disease may be characterized by the presence of specific autoantibodies.

  • Diagnostic profile to identify the ANCA-associated vasculitides (AAV), also known as small vessel vasculitides: granulomatosis with polyangiitis (GPA; formerly called Wegenerʼs granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA; formerly called Churg-Strauss syndrome)


    ANCA (Anti-Neutrophil Cytoplasmic Ab) by immunofluorescence assay (IFA);

    Anti-MPO (Myeloperoxidase) Ab and Anti-PR-3 (Proteinase 3) Ab by enzyme immunoassays; Depending on staining patterns on ethanol- and formalin-fixed neutrophils, c-ANCA, p-ANCA or atypical p-ANCA is resulted with titers, if positive. Otherwise, ANCA is reported as negative. Anti-Nuclear Ab (ANA) by IFA is performed if ANCA-positive to rule out false positive ANCA due to the presence of ANA

  • Diagnostic profile designed to identify autoimmune causes of vasculitis including lupus, ANCA-associated vasculitides (AAV) and Anti-GBM disease


    ANA by IFA, ANCA by IFA, Anti-MPO Ab, Anti-PR3 Ab, Anti-GBM Ab, RF by Turbimetry, Anti- dsDNA Ab by Farr (RDL), C3 Complement, C4 Complement

  • Diagnostic profile designed to identify underlying autoimmune causes of glomerulonephritis including lupus, ANCA-associated vasculitides (AAV), and Anti-GBM (glomerular basement membrane) or Goodpasture's disease


    Anti-Nuclear Ab (ANA) by IFA, Anti-Neutrophil Cytoplasmic Ab (ANCA), Anti-Myeloperoxidase Ab (MPO), Anti-Proteinase 3 Ab (PR-3), Anti-GBM Ab, Anti-dsDNA Ab by Farr, C3 Complement, C4 Complement

Gastroenterology Profiles

Novel serological markers for inflammatory bowel disease (IBD) and autoimmune liver disease improve sensitivity and specificity to aid in differential diagnosis and provide valuable prognostic information about disease behavior.

  • Diagnostic profile including the novel Anti-Glycan Ab designed to help differentiate inflammatory bowel disease (IBD) from non-IBD and Crohnʼs disease (CD) from ulcerative colitis (UC)6


    Anti-Glycan Ab: ASCA (Anti-Saccharomyces Cerevisiae Ab, ACCA (Anti-Chitobioside Carbohydrate Ab), ALCA (Anti-Laminaribioside Carbohydrate Ab), AMCA (Anti-Mannobioside Carbohydrate Ab)

  • Diagnostic profile to identify and differentiate between autoimmune hepatitis types 1 and 2


    Anti-Nuclear Ab (ANA) by IFA, ANCA by IFA, Anti-Chromatin Ab, Anti-Liver/Kidney Microsomal Ab, Anti-Mitochondrial M2 EP(MIT3) Ab, Anti-Soluble Liver Ag Ab

 

References

  1. Coffey CM, Crowson CS, Myasoedova E, Matteson EL, Davis JM. Evidence of diagnostic and treatment delay in seronegative rheumatoid arthritis: Missing the window of opportunity. Mayo Clin Proc. 2019;94(11):2241-2248. doi: 10.1016/j.mayocp.2019.05.023. Epub 2019 Oct 13. PMID: 31619364; PMCID: PMC6947665.
  2. Agmon-Levin N, Damoiseaux J, Kallenberg C, et al. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis. 2014;73:17–23. 2014;9(4):e93812-e93812.
  3. Conrad K, Röber N, Andrade LEC, Mahler M. The clinical relevance of anti-DFS70 autoantibodies. Clinic Rev Allerg Immunol. 2017;52:202-216.
  4. Fitch-Rogalsky C, Steber W, Mahler M, et al. Clinical and serological features of patients referred through a rheumatology triage system because of positive antinuclear antibodies. PLoS One. 2014;9(4):e93812.
  5. Panagopoulos P, Goules A, Hoffmann-Vold AM, Matteson EL, Tzioufas A. Natural history and screening of interstitial lung disease insystemic autoimmune rheumatic disorders. Ther Adv Musculoskelet Dis. 2021;13:1759720X211037519.
  6. Bonneau J, Dumestre-Perard C, Rinaudo-Gaujous M, et al. Systematic review: new serological markers (anti-glycan, anti-GP2, anti-GM-CSF Ab) in the prediction of IBD patient outcomes. Autoimmun Rev. 2015;14(3):231-245. doi:10.1016/j.autrev.2014.11.004.
  7. Satoh M, Chan EK, Sobel ES, et al. Clinical implication of autoantibodies in patients with systemic rheumatic diseases. Expert Review of Clinical Immunology. 2007;3(5):721-738. doi:10.1586/1744666X.3.5.721.8.