2 Chakravarty K, McDonald H, Pullar T et al. BSR/BHPR guideline for disease-
phosphokinase and immunoglobulin levels were normal. Liver
modifying anti-rheumatic drug (DMARD) therapy in consultation with the British
function tests were abnormal: aspartate transaminase 219 IU/l
Association of Dermatologists. Rheumatology 2008;47:924–5.
3 University Hospital Birmingham NHS Foundation Trust. A–Z services: rheumatology.
(0–31), alanine transaminase 117 IU/l (0–31), GT 331 IU/l (2–30),
Guidelines for the management of rheumatology patients.
alkaline phosphatase 177 IU/l (30–130), bilirubin 6 mol/l (0–17)
and albumin 27 g/l (33–47). Hepatitis B surface antigen, hepatitis
C antibody, HIV serology were negative and viral studies for CMV,Epstein–Barr virus, Herpes simplex virus and parvovirus did not
indicate acute infection. ANAs (1 : 320), anti-Ro antibodies
(>100 u/ml, normal range 0–20) and anti-thyroid microsomal anti-
bodies were positive. Anti-double-stranded DNA, aCLs, ANCAs,
Complement C1q and C8 deficiency in an individual
anti-mitochondrial and anti-liver/kidney microsomal antibodieswere negative. Percutaneous liver core biopsy showed mild mono-
with recurrent bacterial meningitis and adult-onset
nuclear cell infiltrate in the portal tracts, moderate interface
systemic lupus erythematosus-like illness
hepatitis and focal necrosis and hepatocyte apoptosis withinparenchymal areas, features consistent with autoimmune hepatitis.
SIR, A 49-yr-old nulliparous Caucasoid lady presented with a
Whilst C3 and C4 levels were normal, total complement
several week history of florid oral ulceration, malaise, weight lossand fever. There was no rash, photosensitivity, arthralgia, alo-
haemolytic activity (CH50) was repeatedly absent indicating
poecia, RP, headache, ocular disturbance or recent foreign travel.
possible complement deficiency state. Reconstitution assays were
Past medical history included hypothyroidism associated with
performed in which sera with selective defects of complement
anti-thyroid microsomal antibodies for which she was taking
components or subunits were mixed with the patient sera and the
thyroxine, bacterial meningitis at the age of 21 and 27 yrs and
haemolytic activity of the resultant mixture measured (Table 1).
group A meningococcal septicaemia at the age of 44 yrs. There
Serum deficient in either the C8 subunit of the C8 protein or the
was a family history of consanguinity. She was dehydrated
classical pathway component C1q did not restore haemolytic
with low-grade pyrexia of 37.68
C and had multiple oral aphthous
activity to the patient’s sera. Normal CH50 was only restored
ulcers. ESR was >100 mm/h, CRP 11 mg/l (0–10), Hb 9.4 g/l,
following the addition of both C8 and C1q to the patient’s sera.
mean cell volume 92.1 fl, white cell count 5 Â 109/l, lymphocytes
Antigenic assays confirmed complete absence of both C8 and
1 Â 109/l, platelet count 248 Â 109/l. Renal function, creatinine
C1q in our patient (Table 1). The genetic basis of the C8
Classical pathway haemolytic assays:
Lysis when patient sera added to:
Sera depleted in classical pathway components:
Sera depleted in terminal pathway components:
Alternative pathway haemolytic assays:
Lysis when patient sera added to:
Complement C8 analysis:
Pooled human sera
Genetic basis of C8β deficiency = homozygous R427 Term in exon 9 of C8β gene
Complement C1q analysis:
Pooled human sera
Genetic basis of C1q gene deficiency = homozygous G34R in C1qC genec
aThe concentration of C8 and C1q added to 2 l of patient serum in 200 l diluent was 500 ng; bLMW C1q : lowmolecular weight C1q detected by sucrose gradient ultracentrifugation ; cConfirmed using Sfcl RFLP assay . Aminoacid numbering refers to the translational start site (methionine is one), G: glycine; R: arginine; Term: stop codon.
deficiency was a homozygous null mutation within exon 9 of the
1 Kaufmann T, Hansch G, Rittner C et al. Genetic basis of human complement C8 beta
C8B gene (R427Term, Table 1), a mutation previously identified
deficiency. J Immunol 1993;150:4943–7.
2 Petry F. Molecular basis of hereditary C1q deficiency. Immunobiology 1998;
as the commonest cause of C8 deficiency in Caucasoid
individuals . The C1q deficiency was due to a homozygous
3 Kirschfink M, Petry F, Khirwadkar K et al. Complete functional C1q deficiency
point mutation (G34R) in the first coding exon of the C1qC gene,
a mutation previously identified as a cause of C1q deficiency in
4 Pickering MC, Botto M, Taylor PR et al. Systemic lupus erythematosus, complement
German, Indian and Saudi Arabian families . The G34R
deficiency, and apoptosis. Adv Immunol 2000;76:227–324.
mutation is associated with the presence of an abnormal, non-
5 Tedesco F, Densen P, Villa MA et al. Two types of dysfunctional eighth component
functional C1q protein in circulation (low molecular weight C1q)
of complement (C8) molecules in C8 deficiency in man. Reconstitution of normalC8 from the mixture of two abnormal C8 molecules. J Clin Invest 1983;71:183–91.
 which was detected in our patient (Table 1). Parental DNA was
6 Morgan BP, Walport MJ. Complement deficiency and disease. Immunol Today
not available and no C1q or C8B mutations were present in a
7 Slingsby JH, Norsworthy P, Pearce G et al. Homozygous hereditary C1q deficiency
A diagnosis of SLE-like illness associated with homozygous
and systemic lupus erythematosus. A new family and the molecular basis of C1qdeficiency in three families. Arthritis Rheum 1996;39:663–70.
C1q deficiency was established together with homozygous
8 Walport MJ, Davies KA, Botto M. C1q and systemic lupus erythematosus.
C8 deficiency associated with recurrent bacterial meningitis.
Immunosuppressive therapy with prednisolone and AZA resultedin complete resolution of her transaminitis. AZA therapy was
poorly tolerated, hence maintenance treatment with mycopheno-
late mofetil was started. Three years later she remains in remission
Advance Access publication 18 August 2008
and has not suffered any infective complications.
Homozygous C1q deficiency is a strong susceptibility factor for
Comment on: Infliximab, etanercept and adalimumab for
the development of an SLE-like illness: $93% of C1q-deficient
the treatment of ankylosing spondylitis: cost-effectiveness
individuals developed an SLE-like illness, typically beginning in
childhood and frequently associated with cutaneous vasculitis,glomerulonephritis and cerebritis . Homozygous deficiency of
SIR, The recent editorial by Wailoo et al.  on cost-effectiveness
complement C8 presents with selective deficiency of either C8 or
evidence of TNF-inhibitors in AS is incorrect and worrying in
C8- subunits  and is associated with an increased risk of
recurrent neisserial infections, a feature common to all terminal
First, the critique of the paper by Kobelt et al.  is factually
pathway component deficiencies . To our knowledge, this indi-
wrong. The numbers cited by Wailoo and colleagues are nowhere to
vidual represents the first reported case of combined C1q and C8
be found in this publication, and the ‘mistake’ is thus a
deficiency. It was particularly striking that the onset of the SLE-
construction. The point they make about the flawed review
like illness was considerably later than that reported in individuals
process, and the implicit critique of the reviewers and editors of
lacking C1q alone (median onset 6 yrs) . Moreover, her SLE-
International Journal of Technology Assessment in Health Care is
like illness appeared to be less severe: vasculitis, glomerulone-
not substantiated. Instead, there is reason to ask how this editorial
phritis or cerebritis have been described in C1q-deficient
cleared this journal’s review process.
individuals with the G34R mutation [3, 7, 8]. Thus, we speculated
Second, the authors seem to mix up information that they have
that the inability to develop terminal pathway-mediated tissue
gathered through participation in the NICE review process from
injury (by virtue of the C8 deficiency) could have limited the
a manufacturer submission, and what is actually published as a
extent of SLE-induced organ damage in this individual. The
scientific paper. We have no arguments with the procedure that
scarcity of reports of SLE in individuals with terminal pathway
NICE uses qualified reviewers to scrutinize the models and
deficiency precluded any attempt to determine if the illness
data supplied by the sponsors of the technologies assessed. But the
severity in such cases differed from that seen in complement-
privileged access to information these researchers have should
sufficient SLE patients. However, this unique case supports an
not be used to unfairly criticize and discredit other researchers.
important role for the membrane attack complex in the
It happens now very often that the researchers involved in the
development of tissue injury in SLE.
NICE process publish their finding as separate scientificpapers. This contributes to confusions about what is a NICEapplication and review, and what is a scientific paper. There aregood reasons to keep these two separated, particularly since
reviewers can see all models submitted to NICE, but outside
Co-existing complement C8 deficiency ameliorated the SLE
researchers have no access to the details of NICE models. This is
even more important when the NICE evaluation process has notbeen completed.
In this case, the manufacturer of infliximab submitted an
Disclosure statement: The authors have declared no conflicts of
economic model to NICE and the Assessment Group (AG),
along with the necessary raw data (in confidence) to replicate themodel. Within this process, the AG found a programmingerror. The submission stated that patients withdrawing from
treatment return to baseline and then progress according to
ICKERING , P. MACOR , J. FISH , P. DURIGUTTO , F. BOSSI ,
natural history, but the progression was inaccurately programmed
in this particular arm of the model. The mistake was corrected
1Molecular Genetics and Rheumatology Section, Imperial College,
and a new version submitted. The authors of the editorial
London, UK, 2Department of Physiology and Pathology, University
entered this process at a later stage as members of the
of Trieste, Trieste, Italy and 3Institute of Medical Microbiology and
Decision Support Unit (DSU) commissioned to evaluate the
Hygiene, Johannes Gutenberg-University, Mainz, Germany
assessment process, and thus use confidential information in an
Correspondence to: M. C. Pickering, Molecular Genetics and
Third, the editorial rises issues relating to what could be
Rheumatology Section, Imperial College, London, UK.
considered conflict of interest and the motivations for the
editorial. We understand that the unit at Sheffield University,
CA-MRSA: Public F AQs I CDC Infection Control in HealthcareCommunity-Associated MRSA Information for the PublicThe Centers for Disease Control and Prevention (CDC) has received inquiries about infections withantibiotic-resistant Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]) amongpersons who have no apparent contact with the healthcare system. This fact sheet addres
Parasitosis intestinales Julio Romero González, Miguel Angel López Casado Hospital Universitario Materno Infantil Virgen de las Nieves. Granada Desde un punto de vista etiológico, las parasito-mago dónde se destruye la cubierta del quiste, libe-sis intestinales engloban las parasitaciones del tuborándose los trofozoitos que se localizan en la muco-digestivo producidas por protoz