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

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.

Authors

Institutions

Publication Details

Journal
Lara D. Veeken
Published
2026-10-05
DOI
https://doi.org/10.1093/rheumatology/keag532
Primary Topic
Systemic Lupus Erythematosus Research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Sibel Balcı, Nergis Akay, Betül Sözeri, Sıla Atamyıldız Uçar et al.
Lara D. Veeken
Systemic Lupus Erythematosus Research
article

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

Sibel Balcı, Nergis Akay, Betül Sözeri, Sıla Atamyıldız Uçar, Rabia Miray Kışla Ekinci, Mehmet Yıldız, Büşra Acun, Nuray Aktay Ayaz, Fatih Haşlak, Ayşe Balat, Şengül Çağlayan, Semanur Özdel, Yasemin Demir Yiğit, Kenan Barut, Balahan Bora Makay, Metin Kaya Gürgöze, Banu Çelikel Acar, Süleyman Ekrem Albayrak, Mukaddes Kalyoncu, Seher Şener, Ayşenur Paç Kısaarslan, Halil Kazanasmaz, Oya Köker, Sara Şebnem Kılıç, Seza Özen, Gülcan Özomay Baykal, Dilara Ünal, Özgür Kasapçopur, Sümeyra Özdemir Çiçek, Aslıhan Uzun, Sezgin Şahin, Sevcan Azime Bakkaloglu, Eda Kayhan, Eray Tunce, Burcu Bozkaya Yücel, Yasemin Uğur Es, Lütfiye Koru, Ayşenur Alkaya, Amra Adroviç, Hatice Kubra Zora, Hatice Melisa Kaçmaz, Orhan Nurlu, Büşra Başer Taşkın, Aybuke Alisan
article en

Abstract

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.

Lara D. Veeken
Dicle University (TR), Bursa Uludağ Üni̇versi̇tesi̇ (TR), University of Turku (FI), Karadeniz Technical University (TR), University of Health Science (KH), Dokuz Eylül University (TR), Mardin Artuklu University (TR), Turku University Hospital (FI), Antalya Eğitim ve Araştırma Hastanesi (TR), Ümraniye Eğitim ve Araştırma Hastanesi (TR), Istanbul University-Cerrahpaşa (TR), Samsun University (TR), Başkent University Hospital (TR), Sağlık Bilimleri Üniversitesi (TR), Diyarbakır Gazi Yaşargil Eğitim ve Araştırma Hastanesi (TR), Cukurova University (TR), Istanbul Medeniyet University (TR), Gaziantep University (TR), Hacettepe University (TR), Istanbul University (TR), Marmara University (TR), University of Health Sciences Antigua (AG), Erciyes University (TR), Gazi University (TR)
Openalex Percentile: Top 11%
Systemic Lupus Erythematosus Research
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.