Background and Aims C1q nephropathy is an immune glomerular disease in which dominant C1q electron-dense deposits are identified in the mesangium.It commonly presents with nephrotic syndrome, while nephritic syndrome or isolated haematuria are less common. Biopsy findings vary, from no glomerular lesion identified as in minimal change disease (MCD) to focal segmental glomerulosclerosis (FSGS) and immune-mediated proliferative glomerulonephritis. Steroids are the mainstay and other agents have been tried. Rituximab is an anti-CD 20 human/mouse chimeric monoclonal antibody and one of the drugs used in managing C1q nephropathy. We present 3 cases of biopsy-proven C1q nephropathy that presented with nephrotic syndrome. They responded initially to steroids and achieved remission after treatment with rituximab. Method Case Scenarios: Case (1): A 30-year-old man had been diagnosed with steroid sensitive nephrotic syndrome since he was 18 months. Renal biopsy confirmed the diagnosis of C1q nephropathy, more in the spectrum of MCD. He was managed with steroids, and rituximab in 2011 and achieved remission for the last 7 years after 5 doses. His renal function had always remained normal. He presented to our department in 2020 with another relapse and heavy proteinuria (urine protein creatinine ratio (UPCR) was 1300 mg/mmol) but unchanged renal function. Repeat kidney biopsy showed C1q nephropathy in the spectrum of FSGS. He showed good response to oral steroids. On relapse while weaning steroids, Rituximab was considered. He had 2 doses of rituximab of 1 gram 2 weeks apart in July 2021. He achieved full remission over the last 2 years. Case (2): A 77-year-old female presented in 2020 with nephrotic syndrome (UPCR of 660 mg/mmol) and acute kidney injury (AKI) (creatinine 400 μmol/l). Her kidney biopsy showed C1q nephropathy with FSGS features. She was started on haemodialysis due continuous kidney function deterioration. She recovered on steroid therapy to normal kidney function and negative proteinuria, but she relapsed with weaning steroids. So steroid dose was increased and tacrolimus was added. Her renal function remained intact. Following that she had another flare in May 2021 with mild kidney impairment and worse proteinuria (UPCR 500 mg/mmol) while she was on small dose steroid and tacrolimus. She was then started on rituximab. After 2 doses 1 gm 2 weeks apart she achieved remission and her kidney function normalised. She received 2 more doses of 1 gram rituximab 6 months apart with excellent response. She has been in complete remission since. Case (3): A 28-year-old male presented to our department in July 2020 with nephrotic syndrome (urine PCR >900 mg/mmol) and preserved renal function. His kidney biopsy was initially reported as MCD and he was managed with oral steroids. He showed a good response with complete resolution of his proteinuria 3 weeks later and remained in remission for 2 years. However, in August 2022- he suffered a second severe relapse (UPCR 4000 mg/mmol) with preserved renal function. His kidney biopsy was therefore rereviewed and immunofluorescence was added which revealed C1q nephropathy. He had another course of steroids and was initiated on rituximab infusions. He showed full remission after 2 doses (1 gram IV 2 weeks apart) and is on ongoing 6 monthly infusions. Results Rituximab was effective in inducing remission in our patients with nephrotic syndrome due to C1q nephropathy. They were all steroid sensitive. It was effective in both steroid-sensitive and steroid-dependent cases. The first and second cases had biopsy findings in the spectrum of FSGS while the third case histological picture in the spectrum of MCD. They all achieved full resolution of their proteinuria and preserved their renal function finally. Conclusion Rituximab was effective in inducing remission in both steroid-responsive and steroid dependant relapsed patients with C1q nephropathy, despite differences in biopsy results. Kidney function was preserved. More solidified data, including multi-centre randomized controlled trials, are needed to establish clear guidelines for the position of rituximab in the management of the disease and the proper dose to use.

BackgroundThe diagnosis of systemic lupus erythematosis(SLE) relies on autoantibody testing, including double stranded DNA (dsDNA), the testing of which has evolved over time from the FARR assay through to ELISA/ELiA. dsDNA assays can pick up non-specific single stranded DNA as false positives and can give occasional false negative results. To evaluate the implications of this we analysed our hospital’s use of crithidia testing as a confirmatory assay of dsDNA results.ObjectivesInvestigate the relation between dsDNA Abs measured by Crithidia test and ELiA. Define the clinical role for Crithidia testing.MethodsAll crithidia tests for an 8 months from January 2017 to August 2017 were reviewed and results of ANA, ENA, dsDNA and complement collected. Data were collected regarding referral to rheumatology and where possible rheumatology clinic letters were reviewed regarding final diagnosis.ResultsOne hundred and fourcrithidia tests were undertaken of which 91 were negative and 13 positive.Sixteen of the 104 patients were ANA negative, 18 ANA 1:100, 70 ANA >/=1:400, and 14 patients had a positive ENA. Positive crithidias had a dsDNA range from 2 to 333 and negative crithidia from <1 to 131 however positive crithidias were more likely to have higher dsDNA and ANA titres. Of the 65 patients seen by rheumatology 4 did not have available notes for analysis. Ten of the 13 crithidia positive patients were seen by rheumatology, 6 diagnosed as SLE, 1 as TNF induced lupus, 1 MCTD, 1 RA and 1 had no clinical evidence of autoimmune disease. 88 patients were dsDNA positive (cut off of >/=9) of whom 11 were also crithidia positive. Of the 13 positive crithidia results, 2 had a negative dsDNA level, one of whom was ANA 1;400 Ro positive and diagnosed with RA, the other was diagnosed as TNF induced lupus. Of the crithidia negative patients the median dsDNA level was 20, a range of diagnoses were made including 5 patients with SLE who had a positive Ro or La, 3 patients with SLE who were ENA negative, 4 UCTD, 2 MCTD, 2 with GCA/PMR, 3 with RA and 5 with inflammatory arthropathy. Twenty patients were documented as having no evidence of connective tissue disorders (CTDs),others remain under assessment.ConclusionWe have shown a significant number of patients using our ELiA assay are dsDNA positive and crithidia negative. In patients with crithidia positivity autoimmune disease is more likely to be diagnosed. Crithidia testing appears to influence whether or not a patient will be referred to rheumatology, with negative crithidias less likely to be referred. This highlights some of the limitations of dsDNA ELISA testing however there is a clear role for this assay as depicted above in preventing over diagnosis of CTDs and unnecessary commitment to immunosuppression.Disclosure of InterestsNone declared