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Publications

Journal Article Ahead of print

PubMed: 42834437 DOI: 10.1093/rheumatology/keag532

Performance of lupus classification criteria in monogenic lupus: a national multicenter cohort study.

Rheumatology (Oxford)

Authors: Nergis Akay, Sezgin Sahin, Sila Atamyildiz Ucar, Aybuke Alisan, Eray Tunce, Eda Kayhan, Yasemin Ugur Es, Aysenur Alkaya, Busra Baser Taskin, Dilara Unal, Lutfiye Koru, Hatice Kubra Zora, Aslihan Uzun Bektas, Melisa Kacmaz, Halil Kazanasmaz, Sengul Caglayan, Seher Sener, Busra Acun, Gulcan Ozomay Baykal, Yasemin Yigit Demir, Suleyman Ekrem Albayrak, Burcu Bozkaya, Orhan Nurlu, Mehmet Yildiz, Amra Adrovic, Kenan Barut, Sevcan A Bakkaloglu, Metin Kaya Gurgoze, Ayse Balat, Fatih Haslak, Balahan Bora, Sara Sebnem Kilic, Mukaddes Kalyoncu, Oya Koker, Semanur Elmas, Nuray Aktay Ayaz, Seza Ozen, Banu Celikel Acar, Sumeyra Ozdemir Cicek, Sibel Balci, Aysenur Pac Kisaarslan, Rabia Miray Kisla Ekinci, Betul Sozeri, Ozgur Kasapcopur

Affiliations

  • Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Türkiye.
  • Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Türkiye.
  • Department of Pediatric Rheumatology, Cukurova University Faculty of Medicine, Adana, Türkiye.
  • Department of Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Türkiye.
  • Department of Pediatric Rheumatology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Türkiye.
  • Department of Pediatric Rheumatology, University of Health Sciences, Etlik City Hospital, Ankara, Türkiye.
  • Department of Pediatric Rheumatology, Istanbul University Faculty of Medicine, Istanbul, Türkiye.
  • Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Türkiye.
  • Department of Pediatric Rheumatology, Istanbul Medeniyet University Faculty of Medicine, Istanbul, Türkiye.
  • Department of Pediatric Immunology and Rheumatology, Uludag University Faculty of Medicine, Bursa, Türkiye.
  • Department of Pediatric Rheumatology, Dokuz Eylul University Faculty of Medicine, Izmir, Türkiye.
  • Department of Pediatric Rheumatology, Diyarbakır Children's Hospital, Diyarbakır, Türkiye.
  • Department of Paediatric Rheumatology, Karadeniz Technical University Faculty of Medicine, Trabzon, Türkiye.
  • Department of Pediatric Rheumatology, Antalya Training and Research Hospital, Antalya, Türkiye.
  • Department of Pediatric Rheumatology, Adana City Training and Research Hospital, Adana, Türkiye.
  • Department of Pediatric Rheumatology, Gazi University Faculty of Medicine, Ankara, Türkiye.
  • Department of Pediatric Rheumatology, Mardin Training and Research Hospital, Mardin, Türkiye.
  • Department of Pediatric Rheumatology, Gazi Yasargil Training and Research Hospital, Diyarbakır, Türkiye.
  • Department of Pediatric Rheumatology, Fırat University Faculty of Medicine, Elazığ, Türkiye.
  • Department of Pediatric Rheumatology, Samsun Training and Research Hospital, Samsun, Türkiye.
  • Department of Pediatric Rheumatology, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye.
  • Department of Pediatric Rheumatology, Marmara University Faculty of Medicine, Istanbul, Türkiye.
  • Department of Pediatric Rheumatology, Dicle University Faculty of Medicine, Diyarbakır, Türkiye.

Abstract

OBJECTIVES

With advances in genetic testing, monogenic lupus is increasingly recognized, yet disease-specific classification criteria are lacking. We compared all three classification criteria sets in the same monogenic lupus cohort and, for the first time, evaluated their performance across distinct genetic pathways.

METHODS

This national multicenter study included 88 genetically confirmed monogenic lupus patients from 22 pediatric rheumatology centers across Türkiye. Fulfilment of the ACR-1997, SLICC-2012, and EULAR/ACR-2019 criteria and pathway-based differences in classification performance were assessed.

RESULTS

Overall, 74% (n = 65) fulfilled ACR-1997, 70.5% (n = 62) SLICC-2012 and EULAR/ACR-2019 criteria, and 62.5% (n = 55) met all three, whereas 17% (n = 15) met none. Agreement was substantial (κ = 0.63-0.73), with no significant differences between criteria (p > 0.05). Classification performance differed significantly across genetic pathways (p < 0.05), with the highest fulfilment performances in complement deficiencies and the lowest in nucleic acid metabolism and type I interferon pathway defects. Most patients who did not fulfill any classification criteria had nucleic acid metabolism and clearance defects (13/15, 86.7%). Domain-level analyses showed that classification success was mainly driven by mucocutaneous, immunologic, and renal domains. Complement and immune-regulation defects showed a more classical lupus phenotype, with most fulfilling all three criteria (78.6%, 22/28 and 77.8%, 14/18), whereas the proportion was lower in type I interferon pathway and nucleic acid metabolism and clearance defects (33.3%, 2/6 and 47.2%, 17/36). No classification criteria was superior within genetic pathways.

CONCLUSIONS

One-third of genetically confirmed monogenic lupus patients remained unclassified, particularly those with interferon-related and nucleic acid metabolism defects, highlighting pathway-dependent limitations of current classification criteria.

MeSH

Cohort Studies, Classification, Rheumatic Diseases, Nucleic Acids