دورية أكاديمية
Complement C1s deficiency in a male Caucasian patient with systemic lupus erythematosus: a case report.
| العنوان: | Complement C1s deficiency in a male Caucasian patient with systemic lupus erythematosus: a case report. |
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| المؤلفون: | Kleer JS; Laboratory of Clinical Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.; Division of Internal Medicine, University Hospital, Basel, Switzerland., Skattum L; Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, and Clinical Immunology and Transfusion Medicine, Region Skåne, Lund, Sweden., Dubler D; Laboratory of Clinical Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland., Fischer I; Division of Pathology, Cantonal Hospital Aarau, Aarau, Switzerland., Zgraggen A; Division of Rheumatology, Cantonal Hospital Aarau, Aarau, Switzerland., Mundwiler E; Division of Laboratory Medicine, Cantonal Hospital Aarau, Aarau, Switzerland., Kim MJ; Division of Nephrology , Cantonal Hospital Aarau, Aarau, Switzerland., Trendelenburg M; Laboratory of Clinical Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.; Division of Internal Medicine, University Hospital, Basel, Switzerland. |
| المصدر: | Frontiers in immunology [Front Immunol] 2024 Feb 26; Vol. 14, pp. 1257525. Date of Electronic Publication: 2024 Feb 26 (Print Publication: 2023). |
| نوع المنشور: | Case Reports; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Complement C1s*/deficiency , Hereditary Complement Deficiency Diseases* , Lupus Erythematosus, Systemic*/complications , Lupus Erythematosus, Systemic*/diagnosis , Lupus Erythematosus, Systemic*/genetics , Lupus Nephritis*/diagnosis , Lupus Nephritis*/genetics, Adult ; Humans ; Male ; Codon, Nonsense ; Complement C1q/genetics ; Nucleotides ; Reinfection |
| مستخلص: | Deficiencies of the early complement components of the classical pathway (CP) are well-documented in association with systemic lupus erythematosus (SLE) or SLE-like syndromes and severe pyogenic infections. Among these, complete C1s deficiency has been reported in nine cases so far. Here, we describe a 34-year-old male patient who presented with severe, recurrent infections since childhood, including meningitides with pneumococci and meningococci, erysipelas, subcutaneous abscess, and recurrent infections of the upper airways. The patient also exhibited adult-onset SLE, meeting 7/11 of the ACR criteria and 34 of the 2019 EULAR/ACR classification criteria, along with class IV-G (A) proliferative lupus nephritis (LN). A screening of the complement cascade showed immeasurably low CH50, while the alternative pathway (AP) function was normal. Subsequent determination of complement components revealed undetectable C1s with low levels of C1r and C1q, normal C3, and slightly elevated C4 and C2 concentrations. The patient had no anti-C1q antibodies. Renal biopsy showed class IV-G (A) LN with complement C1q positivity along the glomerular basement membranes (GBMs) and weak deposition of IgG, IgM, and complement C3 and C4 in the mesangium and GBM. In an ELISA-based functional assay determining C4d deposition, the patient's absent complement activity was fully restored by adding C1s. The genome of the patient was analyzed by whole genome sequencing showing two truncating variants in the C1S gene. One mutation was located at nucleotide 514 in exon 5, caused by a nucleotide substitution from G to T, resulting in a nonsense mutation from Gly172 (p.Gly172*). The other mutation was located at nucleotide 750 in exon 7, where C was replaced by a G, resulting in a nonsense mutation from Tyr250 (p.Tyr250*). Both mutations create a premature stop codon and have not previously been reported in the literature. These genetic findings, combined with the absence of C1s in the circulation, strongly suggest a compound heterozygote C1s deficiency in our patient, without additional defect within the complement cascade. As in a previous C1s deficiency case, the patient responded well to rituximab. The present case highlights unanswered questions regarding the CP's role in SLE etiopathogenesis. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Kleer, Skattum, Dubler, Fischer, Zgraggen, Mundwiler, Kim and Trendelenburg.) |
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| فهرسة مساهمة: | Keywords: complement C1s; immunodeficiency diseases; lupus nephritis (LN); non-sense mutation; systemic lupus erythematosus (SLE) |
| المشرفين على المادة: | 0 (Codon, Nonsense) 80295-33-6 (Complement C1q) EC 3.4.21.42 (Complement C1s) 0 (Nucleotides) |
| SCR Disease Name: | Complement Component C1s Deficiency |
| تواريخ الأحداث: | Date Created: 20240312 Date Completed: 20240313 Latest Revision: 20240321 |
| رمز التحديث: | 20240321 |
| مُعرف محوري في PubMed: | PMC10925646 |
| DOI: | 10.3389/fimmu.2023.1257525 |
| PMID: | 38469558 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2023.1257525 |