1. P437
Complement deficiency in early-onset lupus: experience from a tertiary care centre in North India
1Sagar Bhattad, 1Amit Rawat, 1Anju Gupta, 1Deepti Suri, 2Martin de Boer, 2Taco W. Kuijpers, 1Surjit Singh
1Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh Blood lab, Blood Cell Research, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands
Introduction
Results
Inherited deficiencies of early complement components of the classical pathway (C1q, C4 and C2) are the strongest risk factors for monogenic forms of lupus
Young age at onset, predominant cutaneous manifestations and unique management strategies
Five children with onset of SLE below 5 years were noted
Male:female ratio - 3:2
Mean age at onset years
Mean duration of illness at the time of enrolment years (0.2 to 9.5 years)
Rash was noted in 80%, renal involvement in one and neurological involvement (cerebral vascular thrombosis with antiphospholipid antibodies) was documented in one.
Anti-nuclear antibodies were detected in all - speckled pattern on indirect immunofluorescence (IIF)
Anti-dsDNA antibodies were negative in all, except one
All children had markedly reduced CH50, 3 had low C1q, while 2 had low C4
Mutations in C1QA gene were noted in all children with low C1q (table)
Objectives
To assay complement C1q, C2, C3 and C4 and CH50 in children with early-onset lupus (onset below 5 years)
Methods
Study setting: Pediatric Rheumatology Clinic, Advanced Pediatrics Centre, PGIMER, Chandigarh
Records of those who had an onset of SLE below 5 years of age were analyzed in detail
Complement components C1q and C2 levels were estimated by enzyme-linked immunosorbent assay (ELISA)
C3 and C4 were measured by end-point nephelometry.
Functional assay for the classical pathway (CH50) was carried out by ELISA.
Mutation analysis of the classical complement pathway proteins was carried out in children with depressed complement levels
Conclusions
Children with early onset lupus (below 5) must be screened for inherited defects of classical complement pathway
Negative anti-dsDNA, speckled pattern of ANA on IIF, normal C3 and C4 with low CH50 in children with lupus warrants a screen for C1q deficiency
Table: Details of children with early onset lupus
Sl. No
Age at onset
Sex
Predominant clinical manifestations
ANA
Anti- dsDNA (IU/ml)
C1q C2 C3 C4
CH 50
Mutation
analysis 1
2.5 M
Cutaneous, CNS
4+ (s)
1.5
0.24 18
1610
420
C1QA (NM_015991) c.622C>T, p.Q208X
Brother of 1 *
Asymptomatic
2+ (s)
0.27 -
1970
400 2 F
Cutaneous
3+ (s)
7.7
0.37 23
2500
500
0.09
C1QA (c.164-2A>C) 3
Muco-cutaneous 6
3.3
156 36
0.1 4
Renal 16 30 47
<3
0.33 5
0.7
109
164 86 10
1.6
(* Asymptomatic, s- speckled pattern on IIF)