Autoantibodies, Cytokines and Chemokines In Serum and Cerebrospinal Fluid Of SLE Patients With Cognitive Dysfunction

Hilda Fragoso-Loyo¹, Alí Duarte-García², Sandra Juárez-Arellano³, Alba Cicero-Casarrubias⁴, Juanita Romero-Díaz⁵, Luis LLorente-Peters¹ and Jorge Sánchez-Guerrero⁶, ¹Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, Mexico, ²Department of Medicine, Tufts Medical Center, Boston, MA, ³Department of Neurology, Instituto Nacional de Ciencias Medicas y Nutricion S.Z., Mexico city, Mexico, ⁴Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, ⁵Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico, ⁶Rheumatology, Mount Sinai Hospital and University Health Network, Toronto Canada, Toronto, ON, Canada

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: autoantibodies, chemokines, Cognitive dysfunction, cytokines and systemic lupus erythematosus (SLE)

Session Information

Title: Systemic Lupus Erythematosus - Clinical Aspects II: Central Nervous System Manifestations, Therapeutics

Session Type: Abstract Submissions (ACR)

Background/Purpose: The nature and pathogenesis and cognitive dysfunction (CD) in patients with SLE is unkown.To determine the presence and levels of autoantibodies, cytokines and chemokines in serum and cerebrospinal fluid (CSF) of SLE patients with CD.

Methods:

40 patients participating in a larger study of CD in SLE were analyzed. All patients are active members in a prospective cohort of SLE of recent-onset at enrollment. At entry into the cohort, patients have a standardized medical history, and laboratory tests. Every 3-6 months, patients are seen for medical care, and disease activity (SLEDAI-2K), medications use/dose are assessed. Every year, information is up-dated; including damage accrual (SLICC-DI), co-morbidities, cardiovascular risk-factors, NPSLE, and a blood sample is drawn. All patients were screened for CD using: Trail Making test, Digit Span, California Verbal Learning test, Rey-Osterrieth complex figure test, the Stroop Color-Word test, WAIS III letter-number sequencing, Animal naming test, Controlled Oral Word association, WAIS-R/III digit symbol substitution test, Grooved pegboard test, and WAIS-R/III similarities. Tests were grouped in 7 cognitive domains: memory, attention/executive function, visuospatial, motor, psycho-motor speed, language, and problem solving. Cognitive Dysfunction was defined as at least -2 SD in 2 or more cognitive domains.

In all patients a blood and CSF sample were drawn and the following autoantibodies were measured: NMDA, nucleosomes, ribosomal-P, ds-DNA, b₂-glycoprotein-I IgG and IgM, anticardiolipin IgG and IgM. Cytokines [Interferon-alpha(IFN- a), Interleukin-6 (IL-6)] and chemokines [monocyte chemoattractant protein-1 (MCP-1), gamma interferon inducible protein-10 (IP-10), Interleukin-8 (IL-8), and CCL-19] were analyzed by luminometry. Results are expressed as pg/mL.

Results:

CD was diagnosed in 10 patients. Patients with CD had median age of 33 years (24 – 57), disease duration 7.0 years, and SLEDAI-2K score 5 (0 – 14) at CD assessment and did not differ from patients without CD.

No difference in autoantibodies, cytokines and chemokines was observed in serum between patients with and without CD.

In CSF, no difference in the levels of autoantibodies and cytokines was observed; however, MCP-1 was significantly higher among patients with CD [886.1 (374.9 – 1439.7) vs. 515.8 (3.2 – 1958.2) pg/mL, p=0.04]. No difference was observed with other chemokines.

Conclusion:

The levels of autoantibodies, cytokines, and chemokines in serum and CSF do not differ between patients with or without CD. Although the levels of MCP-1 in CSF were higher in patients with CD, they do not reach the levels observed in inflammatory NPSLE manifestations. These results support that CD is a non-inflammatory NPSLE manifestation.

Disclosure:

H. Fragoso-Loyo,
None;

A. Duarte-García,
None;

S. Juárez-Arellano,
None;

A. Cicero-Casarrubias,
None;

J. Romero-Díaz,
None;

L. LLorente-Peters,
None;

J. Sánchez-Guerrero,

GlaxoSmithKline,

Bristol-Myers Squibb,

Biogen Idec,

Genentech and Biogen IDEC Inc.,

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