Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single...
Transcript of Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single...
![Page 1: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/1.jpg)
Juan-Manuel Anaya, MD, PhD Center for Autoimmune Diseases Research
Universidad del Rosario Bogota, Colombia
Polyautoimmunity Diagnosis and Significance
![Page 2: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/2.jpg)
Polyautoimmunity
Polyautoimmunity:
Autoimmune diseases (ADs) co-occurring within patients.
Multiple Autoimmune Syndrome : 3 or more ADs in the same patient.
Other terms: “associated”, “overlap syndrome” “coexistent” “secondary”
![Page 3: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/3.jpg)
Multiple Autoimmune Syndromes
Humbert P, Dupond JL. Ann Med Interne Paris 1988;139:159-68.
Three or more well defined autoimmune diseases in a single patient
![Page 4: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/4.jpg)
Polyautoimmunity
Polyautoimmunity in RA, SS, SLE, and other autoimmune diseases.
Factors influencing polyautoimmunity
Does polyautoimmunity influence the severity of autoimmune diseases?
![Page 5: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/5.jpg)
Polyautoimmunity in Rheumatoid Arthritis
• 130/ 955 (13.6%) patients disclosed polyautoimmunity.
• 161 additional ADs were observed. • AITD 76 (8%)
• SS 50 (5.2%)
• SLE 24 (2.5%)
• MAS 23 (2.4%)
• Factors influencing polyautoimmunity in RA : • Familial autoimmunity, Familial RA, and toxics.
• Multiple autoimmune syndrome was associated with extra-articular manifestations.
Anaya JM, et al. EULAR 2015 THU0152
![Page 6: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/6.jpg)
Familial Autoimmunity and Polyautoimmunity in RA
When familial autoimmunity was present, the risk of developing polyautoimmunity was similar in men and women, whereas the risk of polyautoimmunity without FAI
was higher in women than in men.
Anaya JM, et al. EULAR 2015 THU0152
![Page 7: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/7.jpg)
Familial RA and Polyautoimmunity
Anaya JM, et al. EULAR 2015 THU0152
![Page 8: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/8.jpg)
Toxics and Polyautoimmunity in RA
Anaya JM, et al. EULAR 2015 THU0152
![Page 9: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/9.jpg)
Multiple Autoimmune Syndrome and extra-articular manifestations in RA
Anaya JM, et al. EULAR 2015 THU0152
RA RA + 1 Autoimmune Disease
MAS
![Page 10: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/10.jpg)
Rhupus (SLE&RA)
Amaya-Amaya J, et al. Lupus. 2015 Feb 9.
Characteristics of patients with Rhupus (as compared with SLE patients)
• Older
(46.42 ± 13.47 vs. 36.37 ± 13.47 yrs,
p <0.001)
• Later age at onset of the disease
(35.9 ± 15.25 vs. 28.84 ± 12.58 yrs,
p=0.017).
• Similar duration of the disease
(9 ± 7.5 vs. 7.5 ± 7.3 years, p=0.3).
• The mean age at onset of RA was
30 ± 11.63 yrs.
• RA preceded SLE in 15 patients (62.5%).
• The PPV and NPV of anti-CCP3 for
rhupus were 0.62 and 0.91 respectively.
![Page 11: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/11.jpg)
Polyautoimmunity in Systemic Lupus Erythematosus
0%
5%
10%
15%
20%
25%
30%
35%
40%
APS SS AITD
Rojas-Villarraga A, et al. Autoimmun Rev. 2010;9:229-32. Franco J, et al. Clin Endocrinol (Oxf). 2014 Nov 8.
Franco JS, et al. PLoS One. 2014;9:e110242.
![Page 12: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/12.jpg)
Factors Influencing Polyautoimmunity in Systemic Lupus Erythematosus
Variable AOR 95% CI p
Gender (female) 2.30 1.03 5.15 0.043
Articular involvement 2.02 1.26 3.23 0.003
Familial autoimmunity 1.61 1.14 2.28 0.007
Anti-Ro Ab 1.54 1.10 2.16 0.013
Origin (Colombia vs Spain)
1.78 1.40 2.27 < 0.0001
Rojas-Villarraga A, et al. Autoimmun Rev. 2010;9:229-32.
![Page 13: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/13.jpg)
Does ancestry influence polyautoimmunity?
![Page 14: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/14.jpg)
• Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls.
• Marshfield Screening Set 16. 353 STRs, 32 AIMs.
• The individual Admixture map was built using STRUCTURE 2.3.4
• The number of cluster was set in 3, the number of burn-in simulations was set in 5000 and 100000 simulations for inference.
• A MANOVA model on arl transformed ancestral profiles was adjusted to evaluate differences in ancestral profiles among different cases (AD, POLY and MAS) and controls.
Influence of Ancestry on Polyautoimmunity
Molano-González N et al. Submitted
![Page 15: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/15.jpg)
Reference populations and Colombian population.
Ameridian Ancestry Influences Polyautoimmunity
Molano-González N et al. Submitted
Colombian population by autoimmune disease status.
![Page 16: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/16.jpg)
Ameridian Ancestry Influences Polyautoimmunity
Amerindian ancestry European ancestry
p: 0.001 p: 0.003
Molano-González N et al. Submitted
![Page 17: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/17.jpg)
Autoimmune Thyroid Disease in Systemic Lupus Erythematosus
Franco J, et al. Clin Endocrinol (Oxf). 2014 Nov 8.
![Page 18: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/18.jpg)
Sjögren's syndrome and smoking are predictive factors associated with the development of AITD in SLE
Franco J, et al. Clin Endocrinol (Oxf). 2014 Nov 8.
Autoimmune Thyroid Disease in Systemic Lupus Erythematosus
![Page 19: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/19.jpg)
Autoimmune Diseases Prevalence N = 410 (%)
SS alone
275 (67)
SS + AD (Polyautoimmunity)
135 (33)
SS + 1 AD
101 (24.6)
SS + 2 or more ADs (MAS)
35 (8.5)
Polyautoimmunity in Sjögren's Syndrome
Amador-Patarroyo MJ, et al. J Autoimmun. 2012;39:199-205.
![Page 20: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/20.jpg)
Characteristic SS alone
N=276
SS – PA
N=134
p
Disease duration 4 (6) 7.86 (7) 0.003
Age at diagnosis 46.7 ± 14.8 47.9 ± 14.2 0.95
Age at onset 45.4 ± 13.8 43.3 ± 13.3 0.2
Polyautoimmunity in Sjögren's Syndrome N=410
Amador-Patarroyo MJ, et al. J Autoimmun. 2012;39:199-205.
![Page 21: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/21.jpg)
21,5
8,3 7,6
2,6 1,4 1,1 0,7 0,3 0,4 0,4 0,4 0,4
0
5
10
15
20
25
AITD RA SLE APS SSc VAS IBD MS VIT AIH PSO PeA
Autoimmune Disease
Pre
vale
nce
%
Polyautoimmunity in Sjögren's Syndrome
Amador-Patarroyo MJ, et al. J Autoimmun. 2012;39:199-205.
![Page 22: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/22.jpg)
8
7
6 6
0
2
4
6
8
10
SS-AITD-SLE SS-AITD-RA SS-SLE-APS SS-SLE-RA
Polyautoimmunity in Sjögren's Syndrome MAS cases
MAS phenotypes
Pre
vale
nce
Amador-Patarroyo MJ, et al. J Autoimmun. 2012;39:199-205.
![Page 23: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/23.jpg)
Characteristic SS Alone
%
SS-PA
% AOR 95% CI p
Positive smoking
status 27.6 51.5 2.86 1.18-6.94 0.02
Spontaneous
abortions 2.1 17.5 10.87 1.47-80.08 0.02
ANAs (+) 83 93.5 8.55 1-73.05 0.05
Polyautoimmunity in Sjögren's Syndrome
Amador-Patarroyo MJ, et al. J Autoimmun. 2012;39:199-205.
![Page 24: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/24.jpg)
Systemic Sclerosis. 38% Hudson M, et al. J Autoimmun 2008;31:156-9. Elhai M, et al. Autoimmun Rev. 2013;12:1052-7.
Primary Biliary Cirrhosis. 32% Gershwin ME, et al. Hepatology 2005;42:1194-202.
Vitiligo. 27% Amerio P, et al. Eur J Dermatol. 2010;20:354-8.
Myastenia Gravis. 13% Mao ZF, et al. Int J Neurosci 2011;121:121-9.
Autoimmune Thyroid Diseases. 14%
Boelaert K, et al. Am J Med 2010;123:183.e1-9.
Multiple Sclerosis. 8% Deretzi G, et al. Acta Neurol Scand. 2015;131:225-30. Marrie RA, et al. Mult Scler. 2015;21:282-93.
Polyautoimmunity in SSc, PBC, Vitiligo, AITD and MS
![Page 25: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/25.jpg)
Clustering of autoimmune diseases is not random
Anaya et al. Clin Rev Allergy Immunol. 2012;43:256-64.
![Page 26: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/26.jpg)
Polyautoimmunity
Polyautoimmunity in SS, SLE, and other autoimmune diseases
Multiple Autoimmune Syndrome
Factors influencing polyautoimmunity
Does polyautoimmunity influence the severity of autoimmune diseases?
![Page 27: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/27.jpg)
Polyautoimmunity and Severity
Some reports favor severity
• More erosive disease in Rhupus and anti-CCP antibodies
• Higher Incidence of malignancy in RA and SS
• Low rates of remission in MG and AITD
• More severe disease in T1D and celiac disease
• Vasculitis is associated with high SLEDAI score in SLE
• More severity of SLE+APS.
Christensen et al. Acta Neurol Scand 1995;91:192-5. Valerio et al. Diabetologia 2002;45:1719-22.
Ramos-Casals et al. Medicine (Baltimore). 2006;85:95-104. Chan et al. J Rheumatol. 2008 Jan;35:77-83.
Kauppi et al. Cancer Causes Control 1997;8:201-4. Franco JS, et al. PLoS One. 2014;9:e110242.
![Page 28: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/28.jpg)
Polyautoimmunity and Severity
Some reports indicate less severity
• Milder disease in MG and AITD
• Milder disease in SSc and AITD
• SS or AITD do not influence outcome in SLE (nephritis)
Marinó et al. J Clin Endocrinol Metab 1997;82:438-43
Avouac et al. J Rheumatol 2010;37:608-14 Rojas-Villarraga et al. Lupus 2010 19: 150
Franco et al. EULAR 2014
![Page 29: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/29.jpg)
Polyautoimmunity Conclusions
Polyautoimmunity is a frequent condition (10-40%).
Factors associated with polyautoimmunity include gender
(female), familial autoimmunity, tobacco smoking,
ancestry (amerindian).
Based on polyautoimmunity and depending on severity,
autoimmune diseases may be categorized as major and
minor conditions. In this sense, how polyautoimmunity
affects major autoimmune diseases warrants further
investigation.
![Page 30: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/30.jpg)
Polyautoimmunity Conclusions
The assessment and clustering of polyautoimmunity will help to define plausible approaches to studying the common mechanisms of these diseases (i.e., the autoimmune tautology).
Identification of commonalities among autoimmune diseases may provide insights about salient mechanisms that are necessary and perhaps sufficient for autoimmunity to occur.
Polyautoimmunity, as an extreme phenotype of autoimmunity, would be critical for dissecting genes of major effect conferring susceptibility to autoimmunity.
![Page 31: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/31.jpg)
ταυτολογία Rhetoric
From Greek tauto, “the same”;
logos, “word/idea”.
Tautology is an obvious statement.
Logic
Tautology is a formula, which is true in every possible interpretation.
Vpq = AD1 ~ AD2 ~ AD3
Anaya JM. Arthritis Res Ther. 2010;12:147. Anaya JM. Autoimmun Rev. 2012;11:781-4.
Anaya et al. Clin Rev Allergy Immunol. 2012;43:256-64. Anaya et al. Autoimmune Dis. 2012;2012:297193.
![Page 32: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/32.jpg)
• Female predominance • Shared subphenotypes • Polyautoimmunity • Familial aggregation • Age at onset • Similar pathophysiology • Autoimmune ecology • Ancestry and genetic factors • Treatment
The Autoimmune Tautology Common mechanisms of autoimmune diseases
![Page 33: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/33.jpg)
Shared Subphenotypes Among Autoimmune Diseases
• Clinical – Non-erosive arthritis
– Photosensitivity
– Raynaud´s phenomenon
– Alopecia
– Depression
– Cardiovascular disease
• Laboratory – Antinuclear antibodies
– Rheumatoid factor
– Anti-Ro antibodies
![Page 34: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/34.jpg)
Luu VP et al. Autoimmunity 2014;47:1-12. Vadasz Z et al FEBS Lett. 2013;587:2074-8.
Yang M, Cell Mol Immunol 2013;10:122-32. Berthelot JM, et al. Joint Bone Spine 2013;80:18-22.
Imbalance of Regulatory Cells in Autoimmune Diseases
![Page 35: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/35.jpg)
Singh RP, et al Autoimmun Rev. 2014
Th17 Cells in Inflammation and Autoimmunity
![Page 36: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/36.jpg)
• Presence of IFN signature in autoimmune diseases.
• Regulation of MHC expression. • Increased amounts of IFN α. • Activates the Janus kinase
(JAK)-signal transducer and activator of transcription (STAT) pathway, leading to transcription of IFN-stimulated genes (ISGs).
Type 1 interferon is a central factor in Autoimmunity
Ivashkiv LB, Donlin LT. Nat Rev Immunol 2014;14:36-49. Wahren-Herlenius M, Dörner T. Lancet 2013;382:819-31.
![Page 37: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/37.jpg)
IgG anti-EBV
Epstein–Barr virus and Autoimmune Diseases
Anaya et al. Autoimmunity. From bench to bedside. 2013
![Page 38: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/38.jpg)
Primary Biliary Cirrhosis
Systemic Lupus Erythematosus
Autoimmune Thyroid Disease
Rheumatoid Arthritis
Smoking is a risk factor for autoimmune diseases and their severity
Multiple Sclerosis Brix TH, et al. Arch Intern Med. 2000;160:661-6. Belbasis L, et al. Lancet Neurol. 2015;14:263-73. Juran BD, et al. Semin Liver Dis. 2014;34:265-72.
Costenbader KH, Karlson EW. Lupus 2006;15:737-45. Di Giuseppe D, et al. Arthritis Res Ther. 2013;15:R56.
![Page 39: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/39.jpg)
The genetic factors for
autoimmune diseases consist
of 2 forms: those common to
many diseases and those
specific for a given disorder.
![Page 40: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/40.jpg)
• Female predominance • Shared subphenotypes • Polyautoimmunity • Familial aggregation • Age at onset • Similar pathophysiology • Autoimmune ecology • Ancestry and genetic factors • Similar treatment
The Autoimmune Tautology Common mechanisms of autoimmune diseases
![Page 41: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/41.jpg)
Polyautoimmunity Conclusions
Identification of commonalities among ADs may provide insights about salient mechanisms that are necessary and perhaps sufficient for autoimmunity to occur.
Polyautoimmunity, as an extreme phenotype of autoimmunity, would be critical for dissecting genes of major effect conferring susceptibility to autoimmunity.
![Page 42: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/42.jpg)
HLA-DRB1, HLA-DQB1, CD226, PTPN22, STAT4, GPR103, TNFAIP3, LRP1/STAT6
Polyautoimmunity Genes
![Page 43: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/43.jpg)
Acknowledgments
![Page 44: Polyautoimmunity Diagnosis and Significance · •Population: 508 individuals: 240 single autoimmune disease, 51 with polyautoimmunity, 36 with MAS, and 181 matched-controls. •](https://reader033.fdocuments.net/reader033/viewer/2022050112/5f49418cbc0bae745a389e3a/html5/thumbnails/44.jpg)
Thank you!