Neuroimmunological features in patients with systemic lupus erythematosus

April 8, 2022
1052
Resume

The article is devoted to the neuroimmunological characteristics of patients with systemic lupus erythematosus (SLE). Despite the fact that neurological disorders are a fairly typical manifestation of this disease and are even singled out by some authors as a separate condition — neuropsychiatric SLE, the pathogenesis of their occurrence remains insufficiently elucidated. There is an assumption about two main pathogenetic mechanisms: autoimmune (inflammatory) and vascular. This study is devoted to the study of the first of them.

Aim: to study the role of antibodies with antineuronal properties in the occurrence of neurological manifestations in patients with SLE.

Object and methods of the research. The object of the study were antibodies with possible antineuronal properties in patients with SLE. Laboratory examination involved three different blood tests: an analysis for the presence of antinuclear antibodies (ANA) with the determination of their type and titer, a blood test for the presence of antibodies to cardiolipin (aCL) and a blood test for lupus anticoagulant (LA).

Results. A comprehensive examination of 64 patients with SLE, who were treated in the department of rheumatology and the department of nephrology of the Dnipropetrovsk Regional Clinical Hospital during 2018–2021, was carried out. Neurological disorders were diagnosed in 54 (84.4%) participants, these patients were included in the main study group. In 10 (15.6%) individuals, these manifestations were not found and they were included in the comparison group. A blood test for the detection of LA was performed by the coagulometric method and included two tests: screening (LA1) and confirmatory (LA2) and further calculation of the ratio of these two tests — LA1/LA2. Based on the results of this ratio, a conclusion was made about the presence or absence of LA in the patient’s blood, as well as the severity of the positive result. A negative result was detected in 23 patients (in 16 (29.6%) of the main group and in 7 (70.0%) of the comparison group) (p=0.002). A blood test for the presence of aCL was carried out by enzyme immunoassay. According to the results of this study, the presence of this type of antibody was found in 29 participants in the main group and was not found at all in the comparison group (p=0.002). According to the results of the analysis for the determination of ANA, it was found that the most common type of ANA in patients with neurological manifestations (main group) were antibodies to double- and single-stranded DNA, histones and nucleosomes, antibodies to the nucleoplasm (anti-SS-A, anti-SS-B) and antibodies to the ribosomal protein P, whereas in the participants of the comparison group, antibodies to the nuclear membrane and antibodies to double- and single-stranded DNA, histones and nucleosomes were predominantly detected, and the titers of these antibodies were significantly lower than in patients of the 1st group (p<0.001). Numerous correlations were also found between the detection of individual antibodies and various clinical and paraclinical findings.

Conclusions. Neurological symptoms are one of the most common manifestations of SLE. The most common types of autoantibodies associated with neurological symptoms are aCL, LA, and some ANA subtypes. These antibodies can be used in the future to develop an algorithm for diagnosing neurological disorders in SLE patients and to build a prognostic model for these disorders.

References

  • 1. Unterman A., Nolte J.E.S., Boaz M. et al. (2011) Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. In Semin. Arthritis Rheum., 41(1): 1–11.
  • 2. Ainiala H., Loukkola J., Peltola J. et al. (2001) The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology, 57(3): 496–500.
  • 3. Bertsias G.K., Boumpas D.T. (2010) Diagnosis and management of neuropsychiatric SLE manifestations. Nat. Rev. Rheumatol., 6(6): 358–367.
  • 4. Borowoy A.M., Pope J.E., Silverman E. et al. (2012) Neuropsychiatric lupus: the prevalence and autoantibody associations depend on the definition: results from the 1000 faces of lupus cohort. In Semin. Arthritis Rheum., 42(2): 179–185.
  • 5. Makarov S.O. (2021) Structure of neurological manifestations in patients with systemic lupus erythematosus. Bull. Рrobl. Biol. Med., 159(2): 90–93.
  • 6. American College of Rheumatology (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis and rheumatism, 42(4): 599–608.
  • 7. Jeltsch-David H., Muller S. (2014) Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat. Rev. Neurol.,10(10): 579–596.
  • 8. Sciascia S., Bertolaccini M.L., Roccatello D. et al. (2014) Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review. J. Neurol., 261(9): 1706–1714.
  • 9. Hanly J.G. (2014) Diagnosis and management of neuropsychiatric SLE. Nat. Rev. Rheumatol., 10(6): 338–347.
  • 10. Noureldine M.H., Harifi G., Berjawi A. et al. (2016) Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies? Lupus, 25(13): 1397–1411.
  • 11. Hu C., Huang W., Chen H. et al. (2015) Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus. PLoS One, 10(5): e0126643.
  • 12. Harrison M., Ravdin L., Volpe B. et al. (2004) Anti-NR2 antibody does not identify cognitive impairment in a general SLE population. Arthritis Rheum., 50(9): 596.
  • 13. Husebye E.S., Sthoeger Z.M., Dayan M. et al. (2005) Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus. Ann. Rheum. Dis., 64(8): 1210–1213.
  • 14. Omdal R., Brokstad K., Waterloo K. et al. (2005) Neuropsychiatric distur-bances in SLE are associated with antibodies against NMDA receptors. Eur. J. Neurol., 12(5): 392–398.
  • 15. Lapteva L., Nowak M., Yarboro C.H. et al. (2006) Anti-N-methyl-D-aspar-tate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum., 54(8): 2505–2514.
  • 16. Govoni M., Bortoluzzi A., Padovan M. et al. (2016) The diagnosis and clinical management of the neuropsychiatric manifestations of lupus. J. Autoimmun., 74: 41–72.
  • 17. Hirohata S., Sakuma Y., Yanagida T., Yoshio T. (2014) Association of cere-brospinal fluid anti-Sm antibodies with acute confusional state in systemic lupus erythematosus. Arthritis Res. Ther., 16(5): 1–9.
  • 18. Gulati G., Iffland P.H., Janigro D. et al. (2016) Anti-NR2 antibodies, blood- brain barrier, and cognitive dysfunction. Clin. Rheumatol., 35(12): 2989–2997.
  • 19. Abbott N.J., Mendonca L.L., Dolman D.E. (2003) The blood-brain barrier in systemic lupus erythematosus. Lupus, 12(12): 908–915.
  • 20. Zaccagni H., Fried J., Cornell J. et al. (2004) Soluble adhesion molecule levels, neuropsychiatric lupus and lupus-related damage. Frontiers in Bioscience, 9: 1654–1661.