Association between the presence of anti-c1q antibodies and active nephritis in patients with systemic lupus erythematosus

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). A retrospective analysis was carried out on a group of 24 patients with SLE to evaluate whether the presence of anti-C1q antibodies (anti-C1q) is related to renal involvement and to explore the behaviour of anti-C1q with respect to LN during a four-year follow-up period. A first serum sample stored at the serum bank, taken not more than three years after SLE diagnosis and one serum sample per year for the subsequent four years were used to detect anti-C1q. Lupus clinical manifestations and serological markers of activity corresponding to the date of each serum sample selected were collected from medical records. In the first serum sample, anti-C1q were found in 8 active SLE. LN was confirmed by histology in 5/8 patients who were positive for anti-C1q and in 1/16 patients who were negative for these autoantibodies (p = 0.0069). Three patients (3/8) had anti-C1q without renal involvement but with lupus skin manifestation. Anti-C1q levels decreased in 3/5 patients with LN who responded to treatment and remained higher in 2/5 patients who needed a new renal biopsy which showed severe renal disease. The 15 patients without severe kidney disease and anti-C1q negative at diagnosis did not develop LN and anti-C1q remained negative in the 4 years of follow up. Anti-C1q were found in SLE patients with active renal involvement or with lupus skin disease. The absence of anti-C1q seemed to be linked to low probabilities of renal involvement.

La nefritis lúpica (NL) es una complicación grave del Lupus Eritematoso Sistémico (LES). Se analizó retrospectivamente en 24 pacientes con LES si la presencia del anticuerpo anti-C1q (anti-C1q) se asociaba con NL y el comportamiento del anti-C1q respecto a la NL en un período de seguimiento de cuatro años. El anti-C1q se determinó en una primera muestra de suero no distante en más de tres años del diagnóstico de LES y en una muestra por año en los siguientes cuatro años. Se obtuvo información de las historias clínicas, sobre manifestaciones clínicas de LES y marcadores serológicos de actividad para las fechas de selección de cada suero. En la primera muestra de suero se detectó anti-C1q en 8 pacientes con LES activo. NL fue confirmada por histología en 5 de ellos y en uno de 16 pacientes con anti-C1q negativos (p = 0.0069); 3 de 8 pacientes fueron anti-C1q positivos sin NL y con lesiones en piel. Los niveles de anti-C1q disminuyeron en 3/5 pacientes con NL que respondieron al tratamiento y se mantuvieron aumentados en 2/5 que necesitaron una nueva biopsia, que evidenció compromiso renal grave. Los 15 pacientes sin enfermedad renal grave y con anti-C1q negativo al diagnóstico no desarrollaron NL y el anti-C1q se mantuvo negativo en los 4 años de seguimiento. El anti-C1q se asoció en pacientes con LES a NL activa o con compromiso en piel. La ausencia del anti-C1q parecería relacionarse a un menor riesgo de desarrollar nefropatía lúpica.

Light chain immunofluorescence in various nephropathies.

Context: Light chain immunofluoresence (IF) in renal biopsy is routinely used in the diagnosis of light chain deposition disease (LCDD), amyloidosis and cast nephropathy. Light chain predominance has also been reported in certain glomerulopathies like IgA nephropathy. However, pathogenesis of this pattern of deposition in various glomerulopathies is uncertain. Aim: To discuss the pathogenesis and utility of light chain IF in nephropathies. Setting and Design: Retrospective study. Materials and Methods: The pattern of light chain IF and light microscopic diagnosis in 306 cases of various nephropathies was reviewed. Direct IF was done in all these cases with commercial fluorescence (Fluoresciene Isothiocynate ) conjugated polyclonal rabbit anti-human antisera against IgM, IgG, IgA, C3, C1q, kappa and lambda light chains. Results: Light chain deposits were seen in 240 (78.43%) cases. In IgA nephropathy, lupus nephritis and post-infectious glomerulonephritis (PIGN), lambda positivity was more as compared to kappa. Light chain deposits in LCDD and membranous nephropathy were more kappa type. The IF pattern in amyloidosis was not consistent. Conclusion: The pathogenesis of light chain predominance in glomerulopathies is not clear and it depends on isoelectric point and size of the immune complex. Light chain IF should be performed routinely in all the renal biopsies.

Nefropatía C1q en un paciente de 17 años: caso clínico / C1q nephropathy: report ofone case

Clq nephropathy (Clq N) is an infrequent disease and only about 100 cases have been reponed. It is defined by a pattern of immunofluorescense (IF) with dominant or co-dominant complement Clq with electrondense deposits in the mesangium, without clinical or serological features of Lupus Nephritis. The most common histopathological findings of ClqN are focal segmental glomerulosclerosis and Minimal Change Disease. We repon a 17 year-old male patient with an isolated selective proteinuría found in a routine study. He had normal renal function and uriñe culture was negative. Serum lipids, liver enzymes an complement were all normal. Serum antinuclear and anti-DNA antibodies, antineutrophil cytoplasmic antibodies (ANCA), HIV, Hepatitis B and C serology, were negative. Renal and abdominal ultrasonography was normal. The histopathological study revealed segmental glomerular sderosis, modérate increase of mesangial matrix, Bowmann capsule adhesions and fucsinophil deposits in mesangium. The IF was positive (dominant) for Clq (+++) and IgA, IgG, IgM, C3++, all of them with a granular mesangial distribution. Ultrastructural findings were pedicelar effacement and paramesangial electrondense deposits. Tubular reticular inclusions (TRI) were not found. Remission of proteinuría was reached after 18 months of treatment with enalapril and losartan. The patient remains with normal renal function. Clinical findings, negative serology for Lupus, light microscopy IFwith dominant positivity for Clq, absence of TRI and paramesangial electrondense deposits in electron microscopy lead us to the diagnosis of ClqN. A poor response to steroid therapy was described in ClqN. Thus it was worthwhile to differentiate it from lupus nephritis, that is responsive to steroids.