J Rheum Dis.  2024 Jul;31(3):143-150. 10.4078/jrd.2023.0065.

Clinical characteristics and prognostic value of autoantibody profile in children with monogenic lupus

• Al-Mayouf SM
• Hamad A
• Kaidali W
• Alhuthil R
• Alsaleem A

• KMID: 2557383
• DOI: http://doi.org/10.4078/jrd.2023.0065

Abstract

Objective
To report the frequency of selected autoantibodies and their associations with clinical features in Arab children with monogenic lupus.
Methods
This study was retrospective single-center study of genetically confirmed monogenic lupus cases at childhood lupus clinic at King Faisal Specialist Hospital and Research Center, from June 1997 to July 2022. We excluded familial lupus without genetic testing and patients with insufficient data. Collected data comprised clinical and laboratory findings, including the autoantibody profile, which included the anti-double-stranded DNA (anti-dsDNA), anti-Smith, anti–Sjögren's-syndrome-related antigen A (anti-SSA), anti–Sjögren's-syndrome-related antigen B (anti-SSB), and antiphospholipid (APL) antibodies. Also, disease activity and accrual disease damage were collected at the last follow-up visit.
Results
This study enrolled 27 Arab patients (14 males) with a median age of 11 years (interquartile range 8.0~16 years), with 63% having early-onset disease. The consanguinity rate and family history of lupus were high (74.1% and 55.6%, respectively). The most frequent clinical features were hematological (96.3%), fever (81.5%), mucocutaneous lesions (85.2%), and renal (66.7%). The frequency of the APL antibodies was 59.3%, anti-dsDNA was 55.6%, and anti-Smith and anti-SSA were 48.2% and 44.4%, respectively. Moreover, dsDNA antibodies were significantly associated with musculoskeletal complaints (p<0.05). Likewise, both anti-Smith and anti-SSA antibodies were linked to failure to thrive and recurrent infections in the univariate analysis (p<0.05).
Conclusion
Our study reveals autoantibody frequencies and their association with clinical and prognostic in a substantial monogenic lupus cohort. Distinct clinical manifestations and prognosis association with certain autoantibodies support the idea that monogenic lupus is a distinctive form of lupus. Larger studies needed to validate these findings.

Keyword

Autoantibodies; Monogenic lupus; Systemic lupus erythematosus

Reference

1. Harry O, Yasin S, Brunner H. 2018; Childhood-onset systemic lupus erythematosus: a review and update. J Pediatr. 196:22–30.e2. DOI: 10.1016/j.jpeds.2018.01.045. PMID: 29703361.

2. Pan L, Lu MP, Wang JH, Xu M, Yang SR. 2020; Immunological pathogenesis and treatment of systemic lupus erythematosus. World J Pediatr. 16:19–30. DOI: 10.1007/s12519-019-00229-3. PMID: 30796732. PMCID: PMC7040062.

3. Lou H, Ling GS, Cao X. 2022; Autoantibodies in systemic lupus erythematosus: from immunopathology to therapeutic target. J Autoimmun. 132:102861. DOI: 10.1016/j.jaut.2022.102861. PMID: 35872103.

4. Rodsaward P, Chottawornsak N, Suwanchote S, Rachayon M, Deekajorndech T, Wright HL, et al. 2021; The clinical significance of antinuclear antibodies and specific autoantibodies in juvenile and adult systemic lupus erythematosus patients. Asian Pac J Allergy Immunol. 39:279–86.

5. To CH, Petri M. 2005; Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus? Arthritis Rheum. 52:4003–10. DOI: 10.1002/art.21414. PMID: 16320348.

6. Levy DM, Massicotte MP, Harvey E, Hebert D, Silverman ED. 2003; Thromboembolism in paediatric lupus patients. Lupus. 12:741–6. DOI: 10.1191/0961203303lu458oa. PMID: 14596422.

7. Somers E, Magder LS, Petri M. 2002; Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol. 29:2531–6.

8. ter Borg EJ, Groen H, Horst G, Limburg PC, Wouda AA, Kallenberg CG. 1990; Clinical associations of antiribonucleoprotein antibodies in patients with systemic lupus erythematosus. Semin Arthritis Rheum. 20:164–73. DOI: 10.1016/0049-0172(90)90057-M. PMID: 2287941.

9. Hoffman IE, Peene I, Meheus L, Huizinga TW, Cebecauer L, Isenberg D, et al. 2004; Specific antinuclear antibodies are associated with clinical features in systemic lupus erythematosus. Ann Rheum Dis. 63:1155–8. DOI: 10.1136/ard.2003.013417. PMID: 15308527. PMCID: PMC1755119.

10. Jurencák R, Fritzler M, Tyrrell P, Hiraki L, Benseler S, Silverman E. 2009; Autoantibodies in pediatric systemic lupus erythematosus: ethnic grouping, cluster analysis, and clinical correlations. J Rheumatol. 36:416–21. DOI: 10.3899/jrheum.080588. PMID: 19208567.

11. So HC, Gui AH, Cherny SS, Sham PC. 2011; Evaluating the heritability explained by known susceptibility variants: a survey of ten complex diseases. Genet Epidemiol. 35:310–7. DOI: 10.1002/gepi.20579. PMID: 21374718.

12. Alperin JM, Ortiz-Fernández L, Sawalha AH. 2018; Monogenic lupus: a developing paradigm of disease. Front Immunol. 9:2496. DOI: 10.3389/fimmu.2018.02496. PMID: 30459768. PMCID: PMC6232876.

13. Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S, et al. 2008; Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med. 358:900–9. DOI: 10.1056/NEJMoa0707865. PMID: 18204098.

14. Namjou B, Kilpatrick J, Harley JB. 2007; Genetics of clinical expression in SLE. Autoimmunity. 40:602–12. DOI: 10.1080/08916930701510962. PMID: 18075794.

15. Demirkaya E, Sahin S, Romano M, Zhou Q, Aksentijevich I. 2020; New horizons in the genetic etiology of systemic lupus erythematosus and lupus-like disease: monogenic lupus and beyond. J Clin Med. 9:712. DOI: 10.3390/jcm9030712. PMID: 32151092. PMCID: PMC7141186.

16. Aljaberi N, Nguyen K, Strahle C, Merritt A, Mathur A, Brunner HI. 2021; Performance of the new 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus in children and young adults. Arthritis Care Res (Hoboken). 73:580–5. DOI: 10.1002/acr.24430. PMID: 32841547.

17. Al-Mayouf SM, Akbar L, Abdwani R, Ginesi G, Volpi S, Gattorno M, et al. 2022; Performance of the EULAR/ACR 2019 classification criteria for systemic lupus erythematous in monogenic lupus. Clin Rheumatol. 41:2721–7. DOI: 10.1007/s10067-022-06209-9. PMID: 35590114.

18. Brunner HI, Silverman ED, To T, Bombardier C, Feldman BM. 2002; Risk factors for damage in childhood-onset systemic lupus erythematosus: cumulative disease activity and medication use predict disease damage. Arthritis Rheum. 46:436–44. DOI: 10.1002/art.10072. PMID: 11840446.

19. Gutiérrez-Suárez R, Ruperto N, Gastaldi R, Pistorio A, Felici E, Burgos-Vargas R, et al. 2006; A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus. Arthritis Rheum. 54:2989–96. DOI: 10.1002/art.22048. PMID: 16947634.

20. Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. 2004; The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 65:521–30. Erratum in: Kidney Int 2004;65:1132. DOI: 10.1111/j.1523-1755.2004.00443.x. PMID: 14717922.

21. Gilliam BE, Ombrello AK, Burlingame RW, Pepmueller PH, Moore TL. 2012; Measurement of autoantibodies in pediatric-onset systemic lupus erythematosus and their relationship with disease-associated manifestations. Semin Arthritis Rheum. 41:840–8. DOI: 10.1016/j.semarthrit.2011.09.009. PMID: 22177108.

22. Novak GV, Marques M, Balbi V, Gormezano NW, Kozu K, Sakamoto AP, et al. 2017; Anti-RO/SSA and anti-La/SSB antibodies: association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus. Autoimmun Rev. 16:132–5. DOI: 10.1016/j.autrev.2016.12.004. PMID: 27988434.

23. Correa-Rodríguez M, Pocovi-Gerardino G, Callejas-Rubio JL, Ríos-Fernández R, Martín-Amada M, Cruz-Caparrós MG, et al. 2021; Clinical and serological associations of autoantibodies in patients with systemic lupus erythematosus. J Investig Med. 69:1417–25. DOI: 10.1136/jim-2021-001887. PMID: 34183445.

24. Massias JS, Smith EMD, Al-Abadi E, Armon K, Bailey K, Ciurtin C, et al. 2020; Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups. Lupus. 29:474–81. DOI: 10.1177/0961203320909156. PMID: 32233733. PMCID: PMC7528537.

25. Gomes RC, Silva MF, Kozu K, Bonfá E, Pereira RM, Terreri MT, et al. 2016; Features of 847 childhood-onset systemic lupus erythematosus patients in three age groups at diagnosis: a Brazilian multicenter study. Arthritis Care Res (Hoboken). 68:1736–41. DOI: 10.1002/acr.22881. PMID: 27014968.

26. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. 2012; Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 64:2677–86. DOI: 10.1002/art.34473. PMID: 22553077. PMCID: PMC3409311.

27. Arroyo-Ávila M, Santiago-Casas Y, McGwin G Jr, Cantor RS, Petri M, Ramsey-Goldman R, et al. 2015; Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort. Clin Rheumatol. 34:1217–23. DOI: 10.1007/s10067-015-2941-y. PMID: 25896533. PMCID: PMC4475431.

28. Alduraibi F, Fatima H, Hamilton JA, Chatham WW, Hsu HC, Mountz JD. 2022; Lupus nephritis correlates with B cell interferon-β, anti-Smith, and anti-DNA: a retrospective study. Arthritis Res Ther. 24:87. DOI: 10.1186/s13075-022-02766-1. PMID: 35436902. PMCID: PMC9014622.