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Hereditary C1q deficiency and secondary Sjögren’s syndrome
  1. E P A H Hoppenreijs1,
  2. P J van Dijken2,
  3. P J Kabel3,
  4. J M Th Draaisma4
  1. 1Department of Paediatrics, University Medical Centre Utrecht, The Netherlands
  2. 2Department of Paediatrics, St Elisabeth Hospital Tilburg, The Netherlands
  3. 3Department of Medical Microbiology, St Elisabeth Hospital Tilburg, The Netherlands
  4. 4Department of Paediatrics, University Medical Centre Nijmegen, The Netherlands
  1. Correspondence to:
    Dr E P A H Hoppenreijs
    Department of Paediatrics, University Medical Centre Utrecht, Wilhelmina Kinderziekenhuis, PO Box 85090, 3508 AB Utrecht, the Netherlands;

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A 13 year old Turkish boy with a known C1q deficiency and SLE-like disease developed recurrent parotitis. Investigations confirmed a secondary Sjögren’s syndrome (SS). As far as we know, the association between C1q deficiency and SS has not been described before. The potential role of C1q in the pathogenesis of SS and systemic lupus erythematosus (SLE) might stimulate further research in understanding the pathogenesis of these and other autoimmune diseases. Screening patients with SS for complement deficiencies, including C1q deficiency, seems indicated.

Deficiency of the complement component C1q is a rare genetic disorder with susceptibility to recurrent infections with polysaccharide encapsulated micro-organisms and a high prevalence of autoimmune phenomena, most often SLE.


At the age of 4 years a boy of consanguineous Turkish descent had meningitis of unknown origin. At the age of 8 years he presented with meningococcal sepsis and meningitis. In the late convalescent phase of this infection he developed arthritis of his right elbow and pericarditis. At the age of 10 years he was admitted owing to lobular pneumonia. Immunological studies at that time demonstrated no functional or antigenic activity of C1q based on a homozygous Glu-86 stop mutation in the C1qA gene exon 2. Both parents and a sibling sister were found to be asymptomatic heterozygous carriers. His sibling brother, who also developed SLE-like symptoms, was homozygous for this mutation.

At the age of 13 years the patient developed recurrent arthritis of the ankle and elbow. Two years later he presented with six episodes of alternate right and left parotitis. There were no complaints of dry mouth or dry eyes. Ultrasonography of the parotid gland during an episode of parotitis disclosed diffuse swelling. Salivary scintigraphy showed delayed tracer uptake. Ocular examination showed some corneal erosion, a normal Schirmer test, and a tear break up time of 10 seconds. A salivary gland biopsy showed lymphocytic sialoadenitis with a focus score of 4 and a percentage of plasma cells containing IgA of 9%, consistent with SS. Microscopic haematuria and proteinuria were not present. Immunological studies showed positive antinuclear antibodies (ANA), RNP antibodies, anti-Sm antibodies, anti-SSA antibodies, and a positive rheumatoid factor (RF). Anti-SSB antibodies and anti-dsDNA antibodies were not detected. A direct Coombs test and a serological test for syphilis were negative. Serum immunoglobulins were slightly raised. C3 and C4 were normal.


In our patient a homozygous point mutation in the C1qA gene was demonstrated that has earlier been described in five families from the Slovak republic and Turkey.1 With arthritis, a positive ANA test, and anti-Sm antibodies our patient has an SLE-like disease.2 Patients with SLE commonly have sicca symptoms, which may be related to the concomitant occurrence of SS.3 Secondary SS, in which the disease coexists with an autoimmune disease, is defined by the presence of either ocular or oral symptoms and two of four objective classification criteria.4 Our patient with recurrent swollen salivary glands, autoantibodies to ANA, RF, and SSA, a salivary scintigraphy showing delayed uptake, and biopsy findings consistent with SS, meets the full criteria for secondary SS.

These observations suggest that absence or abnormal function of C1q leads to susceptibility for SLE and SS. This may be due to ineffective immune complex clearance that causes tissue injury, exposes autoantigens, and stimulates an autoantibody response.5 In this respect it is significant that our patient had late onset reactive arthritis and pericarditis related to his meningococcal disease, which is also mediated by immune complexes.6 Other data suggest a defective clearance of apoptotic cells, which promotes accumulation of nucleosomes (suggested antigens in SLE), which in turn drives an autoimmune response.7

In conclusion we report a patient with C1q deficiency, SLE-like disease, and secondary SS. This is the first time that an association between C1q deficiency and SS has been reported. It suggests a role for C1q in the pathogenesis of autoimmune diseases, possibly due to ineffective immune complex clearing or defective apoptosis, and warrants further research.

Screening of patients with C1q deficiency for SS, but especially screening of patients with SS for complement deficiencies, including C1q deficiency, seems indicated.