Patients with Secondary Sjögren’s Syndrome to SLE Are Characterized By Typical Autoantibodies and a Pro-Inflammatory State

Marika Kvarnstrom¹, Guillermo Ruacho², Johanna Gustafsson³, Agneta Zickert⁴, Vilija Oke⁵, Johan Rönnelid⁶, Kerstin Elvin⁷, Iva Gunnarsson⁸ and Elisabet Svenungsson⁸, ¹Unit of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ²Department of Medicine, Unit of Rheumatology,, Stockholm, Sweden, ³Dep. of Medicine, Karolinska Institutet, Karolinska University Hospital, Unit of rheumatology,, Stockholm, Sweden, ⁴Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, ⁵Department of Medicine, Rheumatology Unit, Department of Medicine Solna, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ⁶Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden, ⁷Department of Clinical Immunology and Transfusion Medicine,, 4Unit of Clinical Immunology, Stockholm, Sweden, ⁸Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Clinical, Sjogren's syndrome and cytokines, SLE

Session Information

Date: Tuesday, November 7, 2017

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment Poster III: Therapeutics and Clinical Trial Design

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose :

Sjögren´s syndrome occurs in isolation (primary Sjögren´s syndrome, pSS), but it is also often secondary (sSS) to, and sometimes difficult to delineate from, other rheumatic diseases, in particular from systemic lupus erythematosus (SLE). Consequently there is a need to investigate similarities and differences between SLE patients with (SLE-sSS) and without sSS (SLE-noSS).

Objective s was to investigate the occurrence of sSS in a large cohort of SLE patients and to explore clinical and laboratory characteristics associated with SLE-sSS as compared to SLE-noSS and controls.

Methods:

We included 504 consecutive SLE patients and 322 population controls, individually matched for age and gender to the first patients. All patients fulfilled the 1982 revised ACR criteria for SLE. SLE-sSS was defined according to the American-European consensus criteria (AECC). Accordingly, subjective and objective quantifications of sicca symptoms were recorded on all subjects. All underwent a thorough clinical investigation. SLE-associated autoantibodies, (ANA screening by BioPlex 2200 system, Bio-Rad) and Rheumatoid factor (Rf, Phadia Immunocap 250) were determined with standardized methods for all subjects, Routine laboratory workup and a panel of cytokines (MSD 30-plex cytokine assays, performed on samples from 433 consecutive SLE patients and 319 controls) were measured on fasting blood samples..

Results:

SLE-sSS, as defined by AECC, occurred in 23% of the SLE patients. Compared to SLE-noSS the SLE-sSS group was older, both at inclusion (55 vs 43yrs, p<0.0001) and at disease onset (40 vs. 32 yrs p<0.0001), and more enriched in females (96 vs. 83 %, p=0.0007), patients with leucopenia (57 vs. 45 %, p=0.02) and peripheral neuropathy (15 vs 7 %, p=0.01). Nephritis was less common in SLE-sSS (32 vs 43 %, p= 0.03). Higher levels of total IgG, positivity for anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB antibodies, Rf IgM and Rf IgA further characterized the SLE-sSS group. 20/30 investigated cytokines were detectable, of these 19/20 were higher in SLE than in controls. 6/20 cytokines (TNF-a, IL-6, MCP-4, MIP-1β, IL12/IL-23p40 and IP-10) were upregulated in SLE-sSS vs. SLE-noSS (see table for figures).

Conclusion:

Through strictly applying the AECC criteria we report that the frequency of SLE-sSS increases with age and affects roughly ¼ of SLE patients. Nephritis was less common while leucopenia and peripheral neuropathy were more common among SLE-sSS patients. In addition to excess of well-known SS-associated autoantibodies we report higher levels of six pro-inflammatory cytokines in SLE-sSS as compared to SLE-nonSS. These findings demonstrate that, though often regarded as a milder version of SLE, patients with SLE-sSS are characterized by a state of chronic systemic inflammation.

Immunoglobulins, autoantibodies and pro-inflammatory cytokines

	Controls N=322 median (IQR) or N(%)	SLE-SS N= 117 median (IQR) or N(%)	SLE-noSS N=387 median (IQR) or N(%)	p-value SLE-SS vs. SLE-noSS
IgG total g/L	10.9 (9.5-12.2)	14.5 (10.4-18.3)	12.4(9.8-15.8)	0.009
anti-dsDNA % positive (+)	5(1.6)	36(31.3)	154(41)	0.06
anti-Ro52 % +	3 (0.9)	56(47.9)	84(21.8)	<0.0001
anti-Ro60 % +	5 (1.6)	69(59)	137(35.9)	<0.0001
anti-La/SSB % +	10 (3.1)	44(37.6)	69(18)	<0.0001
Rf IgG % +	10/261(3.8)	17/80(21.2)	35/259(13.5)	0.09
Rf IgM % +	14/283(4.9)	32/83(38.6)	56/281(19.9)	0.0005
TNF-α pg/mL	2.3(2.0-2.8)	4.9 (3.6-7.1)	4.4 (3.0-6.0)	0.008
IL-6 pg/mL	0.5 (0.4-0.7)	1.5 (0.8-3.0)	1.1 (0.6-2.0)	0.009
IL12/IL-23p40 pg/mL	131.2 (99.8-179.5)	211.3 (141.4-363.8)	177.1 (119.6274.5)	0.032
IP-10 pg/mL	351.9 (259.2 -476.4)	808 (536-1911)	726 (440-1471)	0.036

Disclosure: M. Kvarnstrom, None; G. Ruacho, None; J. Gustafsson, None; A. Zickert, None; V. Oke, None; J. Rönnelid, None; K. Elvin, None; I. Gunnarsson, None; E. Svenungsson, None.

To cite this abstract in AMA style:

Kvarnstrom M, Ruacho G, Gustafsson J, Zickert A, Oke V, Rönnelid J, Elvin K, Gunnarsson I, Svenungsson E. Patients with Secondary Sjögren’s Syndrome to SLE Are Characterized By Typical Autoantibodies and a Pro-Inflammatory State [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/patients-with-secondary-sjogrens-syndrome-to-sle-are-characterized-by-typical-autoantibodies-and-a-pro-inflammatory-state/. Accessed .

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