Immune complexes in retinitis pigmentosa.

Abstract

SUMMARY In a group of 46 patients with retinitis pigmentosa (RP) we studied the presence of circulating immune complexes (CIC) and the alterations in the complement system. Our results showed the presence of CIC in 43.5% of the patients studied, reduced levels of the complement components C3 and C4 (p<0-001), and of the haemolytic activity CH50 (p<0-001) when compared with a control group consisting of a 100 healthy subjects. We found a statistically significant correlation between the values of C3 and CIC (p<0-01), C4 and CIC (p<0.01), and between CH50 and CIC (p<0-001). These findings indicate that the CIC may play a role in the pathogenesis of primary retinitis pigmentosa.

Modulation of three key innate immune pathways for the most common retinal degenerative diseases

“…A recent transcriptome study of two advanced stages of RP in dogs showed strongly increased gene expression of inflammasome and complement factors in the retina (Sudharsan et al, 2017). However, earlier studies reported reduced C3 and C4 levels and increased immune complexes in the sera from RP patients, and this reduced systemic complement activity appears to be related to poor disease prognosis (Heredia et al, 1984). The rhodopsin T17M mutation also reduces C3 secretion in RPE cells (Xiong et al, 2017), suggesting that some RP-related genes may regulate complement expression/secretion by RPE cells.…”

Targeting Inflammation in Emerging Therapies for Genetic Retinal Disease

“…However, results have been complicated by the fact that immune reactivity appears to vary amongst RP patients possibly reflecting the genetic heterogeneity of the disease. Studies suggested that circulating immune complexes could be detected in less than 50% of RP patients [50]. This was, however, reported as significant since it correlated with statistically significant reductions of circulating complement factors C3 and C4 and a significant reduction in time taken for RP patient sera to achieve 50% hemolysis of sheep red blood cells [50].…”

“…Studies suggested that circulating immune complexes could be detected in less than 50% of RP patients [50]. This was, however, reported as significant since it correlated with statistically significant reductions of circulating complement factors C3 and C4 and a significant reduction in time taken for RP patient sera to achieve 50% hemolysis of sheep red blood cells [50]. A link with HLA status has also been reported in RP patients [51], and vitreous samples from RP patients have been shown to contain many immune system cells such as various types of lymphocytes [52].…”

Rhodopsin T17M Mutant Inhibits Complement C3 Secretion in Retinal Pigment Epithelium via ROS Induced Downregulation of TWIST1

“…C1q and C3 are involved in synapse elimination as shown by the failure of C1q-and C3-deficient mice to fully refine retinogeniculate connections during postnatal development [Stevens et al, 2007;Stephan et al, 2013]. In addition, clinical evidence showed that C3 level was significantly decreased in RP patients compared to control [Heredia et al, 1984]. It was suggested that the protective effect of C3 may be related to the role of C1q and C3 in the clearance of apoptotic cells from the retina [Humphries et al, 2012].…”

“…C3 plays dual role in different retinal degeneration diseases [Heredia et al, 1984;Cashman et al, 2011]. Reduced levels of complement components C3 and C4 were observed in patients with RP [Heredia et al, 1984]. C3 is expressed in the retinal and RPE/ choroidal tissues, as well as in cultured RPE [Yang et al, 2009;Luo et al, 2011;Luo et al, 2013].…”