AVISE®

Interpretation Guide

Marker (method) Associated Disease Interpretation

EC4d (FACS) 46-66%1

BC4d (FACS)

C3/C4 (IT) 44%

Anti-C1q(ELISA)

60%

Anti-dsDNA IgG(ELISA and IIF)

30-40%3 all

of the

Anti-dsDNA IgG(CIA)

43%

Anti-Nuclear Antibodies (ANA) (ELISA and IIF)

97%

Anti-Ribosomal P (ELISA)

30%

Anti-Smith IgG (ELISA)

Anti-CENP IgG(ELISA)

20-60%7

Anti-Jo-1 IgG(ELISA)

20-30%5

Anti-RNP70(ELISA)

90%

Anti-Scl-70 IgG(ELISA)

28-70%6

A(CIA)

SS S M

Anti-SS-B/La IgG 40-60%8

Anti-U1RNP IgG(ELISA)

95-99%11

X

X

X

X

X

X

X

X

X

X

X

XX

X

X

X

AVISE Interpretation GuideSL

E Ass

ocia

ted

Mar

kers

ENA

Mar

kers

Prevalence

C4d (FACS) %

Marker (method) Associated Disease Prevalence Interpretation

s(ELISA)

SS S M

A(CIA)

A Pol III(ELISA)

S

Anti-Histone(ELISA)

Lupus95%

SLE P

oSL

E Mnit

o

Lupu

s

AVIS

PS

AVISE

CTD

EESIVA

ro E A

r

1

Marker (method) Associated Disease Prevalence Interpretation

Anti-Cyclic Citrullinated Peptide IgG(ELISA)

70-90%12

Rheumatoid Factor IgM & IgA (ELISA)

70-90%12

Associated Disease Prevalence Interpretation

β2-Glycoprotein 1 IgG, IgM & IgA(CIA)

45%

Cardiolipin IgG, IgM & IgA(CIA)

o

97%

Anti-Phosphatidylserine/Prothrombin (PS/PT) IgM & IgG (ELISA)

38-49%1

Marker (method) Associated Disease Prevalence Interpretation

Thyroglobulin IgG(ELISA) 60-85%1 t

Thyroid Peroxidase IgG (ELISA)

71-97%1 t

Thyr

oid

Mar

kers

APS M

arke

rs

X X

RA M

arke

rs

X X

X X

X* X X

2

(ELISA)

- 2

X

Marker (method)

or Underexposed (<200 ng/ml)

AVISE MTXto

AVISE HCQ to

Any of the Following:Anti-Sm > 10 U/mLEC4d > 75 Net MFI

BC4d > 200 Net MFIAnti-dsDNA > 301 U/ML

If Tier 1 is Negative move to Tier 2

Negative

Tier 1

Positive

A deeper look at the AVISE® Lupus two tier algorithm

Tier 2 criteria combines CB-CAPs with additional markers to yield an aggregate index value

Tier 2 generates an index value based on the following components• ANA component• CB-CAPs component•

Tier 2

Tier 1 criteria is highly speci�c for SLE

3

The result for the AVISE Lupus

lotted along a gradient of increasing likelihood for presence of SLE(See page 6 for likelihood ratios)

4

AVISE® CTD and AVISE Lupus result report

Analytes included in Tier 1 and Tier 2 along with respecti ve assessments are reported in two distinct sections

Details for ANA (HEp-2) are at the top of the page including any observed nuclear and cytoplasmic patterns

5

Far left column iden es positive(+) and strong positive(++) interpretations for each analyte

Notes providsummary statements

Call Provider Relations with any questions, or to arrange for a clinical consultation

Notes:

AVISE® CTD and AVISE Lupus page 2

(Note: AVISE SLE Prognostic values will be reported separately)

Provider Relations: 888.452.1522

6

Figure adapted from Putterman et al. Lupus Science & Medicine. 2014.

ll

l

l

l l

P

Sensitivity: 80%Speci�city vs. other disease: 86%

Index Value

www.AviseTest.com | 888.452.1522

eecnecseroulfonummI :AFI ELISA: En yyassA tnebrosonummI dekniL-emy CIA: Chemiluminesc yyassA yassaonummI tne IT: ImmunoturbidimetryMethodology De�nitions: FACS: Fluorescence-Activated Cell SortingReferences:

2020

1. Putterman C, et al. Cell-Bound Complement Activation Products in Systemic Lupus Erythematosus: Comparison with Anti-Double-Stranded Dna and Standard Complement Measurements. Arthritis & Rheumatism. 2014.

2. Wallace D, et al. Systemic Lupus Erythematosus And Primary Fibromyalgia can be Distinguished by Testing for Cell-Bound Complement Activation Products. Lupus Science & Medicine. 2016.3. Wichainun R, et al. Sensitivity and Speci�city of ANA And Anti-Dsdna In The Diagnosis of Systemic Lupus Erythematosus: A Comparison using Control Sera Obtained from Healthy Individuals

and Patients with Multiple Medical Problems. Asian Pac J Allergy Immunol. 2013.4. Migliorini P, et al. Anti-Sm And Anti-Rnp Antibodies. Clinical Immunology Unit, Department Of Internal Medicine. Autoimmunity. 2005.5. Zampieri S, et al. Anti-Jo-1 Antibodies. Autoimmunity. 2005.6. Basu D, et al. Anti-Scl-70. Autoimmunity. 2005. 7. Russo K, et al. Circulating Anticentromere Cenp-A and Cenp-B Antibodies In Patients with Di�use and Limited Systemic Sclerosis, Systemic Lupus Erythematosus, and Rheumatoid Arthritis.

The Journal Of Rheumatology. 2000. 8. Montecucco C, et al. Anti-Ssb/La Antibodies In Sjögren’s Syndrome and Related Autoimmune Diseases. Results of A Quantitative Immunoassay Using a Highly Puri�ed Antigen. Clin Exp

Rheumato.1989.9.

.10.11. Ho�man R, et al. Mixed Connective Tissue Disease. Modern Therapeutics In Rheumatic Diseases. 2002.12. Rantapää-Dahlqvist S, et al. Antibodies Against Cyclic Citrullinated Peptide And Iga Rheumatoid Factor Predict the Development of Rheumatoid Arthritis. Arthritis & Rheumatism. 2003.13. Perches P, et al. Evaluation of Antiphospholipid Antibodies Testing for the Diagnosis of Antiphospholipid Syndrome. Revista Brasileira De Reumatologia. 2009.14. Galli M, et al. Anti–Β2-Glycoprotein I, Antiprothrombin Antibodies, And The Risk Of Thrombosis In The Antiphospholipid Syndrome. Blood. 2003.15. Engler H, et al. Anti-Thyroid Peroxidase (Anti-Tpo) Antibodies in Thyroid Diseases, Non-Thyroidal Illness And Controls. Clinical Validity of a New Commercial Method for Detection of Anti-TPO

(Thyroid Microsomal) Autoantibodies. Clin Chim Acta. 1994.16. Akhter E, et al. Utility of Antiphosphatidylserine/Prothrombin and Iga Antiphospholipid Assays in Systemic Lupus Erythematosus. J Rheumatol. 2013.17. Yin Y, et al. Diagnostic Value of Serum Anti-C1q Antibodies in Patients with Lupus Nephritis: A Meta-Analysis. Lupus. 2012.18. Hanly J, et al. Autoantibodies as Biomarkers for the Prediction of Neuropsychiatric Events In Systemic Lupus Erythematosus. Ann Rheum Dis. 2011.19. Buyon J, et al. Reduction in erythrocyte-bound complement activation products titers of anti-C1q antibodies association with clinical improvement in systemic lupus erythematosus. Lupus

Science of Medicine. 2016.20. Data on �le. Exagen Inc. 2016.21.

2292-2302. 22. et al. with emphasis on skin manifestations and role of 2012 23. Kao A, et al. Relation of platelet C4d with all-cause mortality and ischemic stroke in patients with systemic lupus erythematosus. Transl Stroke Res. 2014 Aug;5(4):510-824. Petri M, et al. Complement C4d Split Products in Combination with Lupus Anticoagulant and Low Complement Associate with Thrombosis in Systemic Lupus Erythematosus [abstract].

Arthritis Rheumatol. 2018; 70 (suppl 10).