1. THU0025
Complement deficiencies in a cohort of pediatric onset lupus: A preliminary study from a tertiary care centre in North India
Sagar Bhattad 1,Amit Rawat 1Surjit Singh 1Anju Gupta 1Deepti Suri 1Ravinder Garg 1Martin de Boer 2T.W. Kuijpers 2
1 Pediatric Allergy and Immunology Unit, Dept of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India, Blood cell Research, Sanquin blood cell foundation, Amsterdam, Netherlands
Introduction
Results
Complement has a potentially dual and paradoxical role in the pathogenesis of systemic lupus erythematosus (SLE).
Inherited homozygous deficiencies of the classical pathway components C1q, C1r/C1s, C4 and C2 are associated with an increased susceptibility to SLE.
Early component components play an important role in the clearance of apoptotic debris generated from dying cells and circulating immune complexes.
Complement deficiencies predispose to the development of SLE due to inefficient disposal of these potentially autoimmunity generating apoptotic cell debris
Mean age at onset of lupus: 9 years (Range 1.5 – 12 years)
Male:Female ratio : 1:3
ANA-IF: put patterns of diff cases
Anti dsDNA was positive in 19/34 (put percentage)
Levels of complements,low in 7/34 children with SLE (features in table).
Distinct clinical and immunological profile in children with complement deficiencies 
Fig 1: Skin rash in a child with C1q deficiency
Fig 2: Speckled pattern of ANA -IF in the same child
Conclusions
Low levels of complement were detected in 7/34 children in our cohort with pediatric onset SLE (during the inactive state of disease).
Children with inherited complement deficiency (C1q, C2 , C4) had an earlier age at onset and distinct clinical and immunological profile.
A child with inherited C1q deficiency (mutation identified) had onset at 2.5 years of age, family h/o lupus in sibling and predominant cutaneous and neurological manifestations (fig 1). ANA had speckled pattern on IIF (fig 2) and anti ds DNA was negative.
Methods
Cross-sectional descriptive study
Cases of pediatric onset systemic lupus erythematosus (pSLE) attending the Pediatric Rheumatology Clinic from January December 2012 were enrolled in the study.
34 cases of pSLE in remission (Low SLEDAI) and 29 age and sex matched controls were enrolled .
Clinical and immunological profile of patients was obtained from hospital records.
C1q, C2 and Anti ds-DNA levels were estimated by ELISA whereas C3 and C4 were determined by end-point nephelometry.
Genetic analysis was carried out in children with depressed levels of these complements.
Statistical Analysis
Comparison of the study and the control
group for levels of individual complement
components C1q, C2 , C3 and C4 was done using Mann Whitney test wherever data had skewed distribution and student T test was used for normal distribution.
Analysis was done using the Statistical Package for Social Sciences (SPSS) Version 20.0 for windows.
Complement deficient
Mutation identified
Clinical features
C1q
Homozygous nonsense mutation:  C1QA  c.622C>T  Q208X
Onset 2.5 years of age.
Cutaneous and neurological manifestations.
Familial SLE
Homozygous accepter splice site mutation at the -2 position also in the C1QA gene
Onset 1.5 years of age
Complement deficient
Age at onset
Sex
Duration of disease
Predominant Clinical features
Anti dsDNA (IU/ml)
C1q C C C4 (50.3) (17.2) (1320) (236)
Mean value in mg/L 1
C1q
2.5 yr M
7.5 yr
CNS and skin.
1.5
0.23
18.2
1610
420 2
1.5 yr F
Skin
7.7
0.37
23.8
2500
500 3
C1q & C4
9.5 yr
5.5 yr
Skin and Joint
1.17
0.7
18.8 30 4 C2
120.5
53.5
8.9
860
160 5
C2 & C4
11.5 yr
Renal
1027
54.6
0.5
650 77 6 C4
9 yr
7 yr
AIHA* 24 60
17.2
1000 7
10.5 yr
Scarring alopecia, Skin.
29.1 67
13.5
1030 75
Table 2: Genetic analysis of children with C1q deficiency
References
Carroll MC. The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol ;16:545-68
Botto M, Walport MJ. C1q, autoimmunity and apoptosis. Immunobiology. 2002;205(4-5):
Holers VM. Complement receptors and the shaping of the natural antibody repertoire. Springer Semin Immunopathol ;26(4):
Table 1: Details of children with low complement levels