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The complement system is part of the innate immune system activated by three distinct pathways: classical, lectin and alternative. It is also involved in retinal development and homoeostasis. Dense deposit disease is a rare renal disease associated with mutations in Complement factor H and overactivity of the alternative complement pathway. As well as glomerulonephritis, many affected individuals have retinal drusen and may be at risk of vision loss due to macular atrophy or choroidal neovascularisation. We discuss the reclassification of dense deposit disease as a type of C3 glomerulonephropathy, and hypothesise on the mechanisms of retinal abnormalities. Drusen have also been described in individuals with other types of glomerulonephritis involving abnormalities of the classical (membranoproliferative glomerulonephritis type 1) or lectin (IgA nephropathy, lupus nephritis) complement pathways. Although drusen are found in abnormalities of all three complement pathways, the age at onset, aetiology, and the threat to vision differs. This review describes drusen and other retinal abnormalities associated with the glomerulonephritides due to abnormal activation in each of the three complement activation pathways, and provides the first report of drusen occurring in a patient with the recently reclassified C3 glomerulonephritis with homozygous variant V62I in complement factor H . Optometric management of young patients presenting with retinal drusen is discussed, and complement-based therapies for visual loss are reviewed.

Many autoantibodies have been described in HIV-infected individuals. We have examined the incidence, associations and prognostic significance of anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies in individuals with HIV infections. One hundred and five patients, with asymptomatic infections (n = 37), AIDS-related complex (n = 32) or AIDS (n = 36) were studied. Plasma from 24 of these (23%) were positive for ANA: most demonstrated speckled fluorescence (n = 21) and were of low titre (1+ in 18). ANCA were demonstrated by IIF in 18 individuals (17%) and all fluorescent patterns were seen; 6 of these plasma were also positive in the ELISAs for antibodies to proteinase 3, myeloperoxidase or elastase. Thirteen plasma were positive for ANCA in the neutrophil cytoplasm ELISA; 10 of these were also positive in the specific ELISAs. A total of 30 plasma bound to proteinase 3, myeloperoxidase or elastase in specific ELISAs, in 6 cases with 2 specificities. Finally, 18 plasma (17%) contained anti-GBM antibodies by ELISA, but none of 4 plasma tested in inhibition assays was specific. ANA, ANCA and anti-GBM antibodies were not uncommon in HIV-infected individuals but the presence of these antibodies was not associated with the clinical manifestations of the corresponding autoimmune diseases. In addition, there was no correlation between the demonstration of these antibodies and the immunological status of the individual (apart from a correlation between CD4 counts less than 400/microliters with anti-GBM antibodies), the presence of an opportunistic infection, the development of malignancy or reduced survival. Some of these antibodies may arise from polyclonal activation, or be due to "sticky" serum since we have shown that the presence of anti-GBM antibodies correlated with the demonstration of ANCA by ELISA. These antibodies are not more common in hypergammaglobulinemic plasma but some may be due to heat-treatment of the plasma. The clinician caring for HIV-infected individuals needs to be aware of these "false-positive" antibody results.

A cutaneous or systemic vasculitis occurs in myelodysplasia as well as in myeloproliferative and lymphoproliferative disorders. The most common lesion is a leucocytoclastic vasculitis, with neurological or joint involvement occurring less often. The vasculitis may appear contemporaneously with or precede the clinical onset of the blood dyscrasia. Occasionally the lesions respond dramatically to the use of steroids but in general, patients with vasculitis have a worse prognosis than those with uncomplicated myelodysplasia. Vasculitis and myelodysplasia appear together too often for the association to be coincidental and the vasculitis in most cases cannot be attributed to intercurrent infections, therapeutic agents or a pre-existing rheumatological disorder. While autoantibodies are frequently present in myelodysplasia, and ANA and anti-neutrophil cytoplasm antibodies (ANCA) are found in other vasculitides, neither of these antibodies is associated with the vasculitis of myelodysplasia. There has however been one report of ANCA in Sweet's syndrome a non-vasculitic skin condition that also occurs in the myelodysplastic syndromes.