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Betegségjelentés · Immunological

Lupus (SLE)

Whole genome sequencing evaluates complement genes (C1Q, C2, C4), interferonopathy genes (TREX1, DNASE1L3, RNASEH2A/B/C), HLA haplotypes (DRB1), and all additional lupus-associated variants, distinguishing monogenic from polygenic lupus.

A betegségjelentés olyan ritka variánsokat keres, amelyekről ismert, hogy okozzák az általa lefedett betegségeket.

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A(z) condition ismertetése

An autoimmune multi-organ disease typically associated with vasculopathy and autoantibody production. Most patients have antinuclear antibodies (ANA). The presence of anti-dsDNA or anti-Smith antibodies are highly-specific.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting approximately 200,000-300,000 people in the US, with ~50% heritability. The genetic architecture includes both polygenic susceptibility (HLA-DR2, HLA-DR3, ITGAM, STAT4, IRF5, BLK, TNFAIP3, and >100 additional GWAS loci) and rare monogenic forms. The strongest common genetic risk factor is the HLA class II region: HLA-DRB1*03:01 and HLA-DRB1*15:01 each confer approximately 2-3 fold increased risk. Copy number variation at C4 (complement component 4) is a major genetic determinant; low C4 copy number substantially increases lupus risk.

Monogenic lupus represents approximately 1-3% of all SLE and is critically important to identify. Complement deficiency, particularly C1q (>90% develop lupus), C1r/C1s, C2, and C4 homozygous deficiency, causes severe early-onset lupus through impaired clearance of apoptotic debris and immune complexes. TREX1 deficiency causes Aicardi-Goutières syndrome/familial chilblain lupus through accumulation of endogenous nucleic acids that activate the type I interferon pathway. DNASE1L3 deficiency causes hypocomplementemic lupus with anti-dsDNA antibodies. These monogenic forms have specific pathogenic mechanisms that influence treatment selection.

Treatment implications of genetic lupus subtyping are emerging. Anifrolumab (Saphnelo), an anti-type I interferon receptor antibody, is FDA-approved for moderate-to-severe SLE and is mechanistically most relevant in patients with high interferon signatures, including those with interferonopathy-pathway variants (TREX1, IFIH1, RNASEH2). Complement-deficient lupus may respond to fresh frozen plasma (replacing the missing complement component) or complement inhibitors, but does NOT respond to standard immunosuppression targeting autoimmune pathways. Belimumab (anti-BLyS) targets B-cell activation and may be particularly effective in patients with BLK or BANK1 risk variants.

C1q deficiency causes lupus in >90% of carriers, the highest penetrance of any lupus gene. This complement-deficiency lupus has a different pathogenic mechanism than autoimmune SLE and may not respond to standard immunosuppressive therapy.

A vizsgált betegség

An autoimmune multi-organ disease typically associated with vasculopathy and autoantibody production. Most patients have antinuclear antibodies (ANA). The presence of anti-dsDNA or anti-Smith antibodies are highly-specific.

Mit változtat a diagnózis

Standard SLE: hydroxychloroquine, mycophenolate, belimumab, anifrolumab; Complement-deficient lupus: FFP replacement; Interferonopathy: anifrolumab, JAK inhibitors; All: sun protection, cardiovascular risk management, pregnancy planning

Vizsgált gének

Más néven

disseminated lupus erythematosus; Lupus; SLE; SLE - lupus erythematosus, systemic; systemic lupus erythematosus (disease); systemic lupus erythematosus susceptibility to

12 kapcsolódó altípust tartalmaz ↓
  • autosomal systemic lupus erythematosus type 16
  • bullous systemic lupus erythematosus
  • central nervous system lupus
  • neonatal lupus erythematosus
  • pediatric systemic lupus erythematosus
  • systemic lupus erythematosus 17
  • systemic lupus erythematosus 18
  • systemic lupus erythematosus related to C1QA
  • systemic lupus erythematosus related to C1QB
  • systemic lupus erythematosus related to C1QC
  • systemic lupus erythematosus related to C1S
  • systemic lupus erythematosus related to C4A
MONDO:0007915OMIM 152700Orphanet 536MedGen 6146

Miért a teljes genom szekvenálás

Monogenic lupus (complement deficiency, interferonopathy) does not respond to standard immunosuppression. Molecular diagnosis identifies the 1-3% of lupus patients who need different treatment, and the emerging genetic biomarkers for targeted therapies like anifrolumab.

Complement-deficient lupus requires complement replacement, not immunosuppression; wrong treatment delays effective therapy for years

C1q-deficient patients produce lupus-like disease through impaired clearance of apoptotic cells and immune complexes, a waste-disposal problem, not a primary autoimmune attack. Standard lupus immunosuppression (mycophenolate, cyclophosphamide) addresses the wrong mechanism. Fresh frozen plasma infusion (providing functional C1q) can produce dramatic clinical improvement. Without genetic complement deficiency testing, these patients receive escalating immunosuppression for 'treatment-resistant lupus', when the correct diagnosis would redirect therapy entirely.

C4 copy number variation is the strongest common genetic determinant of lupus risk: WGS quantifies C4A and C4B gene copies

The C4 locus on chromosome 6 is one of the most structurally complex regions in the human genome; C4A and C4B genes exist in variable copy numbers (0-6 copies each). Low C4 copy number (particularly low C4A) substantially increases lupus risk, while high copy number is protective. Standard genetic testing does not evaluate C4 copy number. WGS reads across the entire C4 locus, enabling copy number quantification that provides the most important common genetic lupus risk assessment.

További immunological conditions

Minden feltétel →

Egy teszt. Egy életen át tartó válaszok.

Egy csomag, házhoz szállítva. Az egész genomját a diagnosztikai döntésekhez használt klinikai színvonalon szekvenáljuk. Orvos számára is használható jelentéseit 6–8 héten belül küldjük el a Genome Manager-be. Ezek tartósan érvényesek, és a tudomány fejlődésével frissülnek.

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