Glomerular Complement Factor H–Related Protein 5 is Associated with Histologic Injury in Immunoglobulin A Nephropathy

Abstract

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Complement activation in IgA nephropathy

“…3). Associations between glomerular FHR5 deposition and histology biomarkers of IgAN severity have been replicated in a cohort of 56 IgAN patients from China [35]. Patients with endocapillary hypercellularity and segmental sclerosis had more intense glomerular FHR5 deposition, and the abundance of glomerular FHR5 correlated with glomerular C3.…”

“…Patients with endocapillary hypercellularity and segmental sclerosis had more intense glomerular FHR5 deposition, and the abundance of glomerular FHR5 correlated with glomerular C3. Also, FHR5 co-localised with IgA and with C3c in glomerular mesangial and capillary areas [35]. Interestingly, kidney immunohistochemistry (IHC) for factor H-related protein 1 (FHR1), which is also predicted to interfere with FH-dependent AP regulation and is linked to the risk of IgAN in genome-wide association studies (see below), did not correlate with IgAN severity [34].…”

Correlation analysis between expression of histone deacetylase 6 and clinical parameters in IgA nephropathy patients

“…Considering that T score is a well-recognized independent predictive indicator of IgAN, it is worth to explore the possible risk factors associated with T. It is reported that tubulointerstitial injury of IgAN was related to p38 mitogen-activated protein kinase activity [ 47 ], serum matrix metalloproteinase-7 (MMP-7) level [ 48 ], trefoil factor 3 mRNA [ 49 ], and H-related proteins 5 (FHR-5) deposition [ 50 ]. In this study, our results showed that the HDAC6 positive area of T1 score and T2 score patients were statistically higher than that of T0 score patients, and associated with lower eGFR.…”

The Contribution of Complement to the Pathogenesis of IgA Nephropathy: Are Complement-Targeted Therapies Moving from Rare Disorders to More Common Diseases?

“…No association was seen between glomerular staining for FHR-1 and IgAN severity. Similarly, a Chinese cohort found mesangial staining of FHR-5 in 57.1% of IgAN cases, and FHR-5 deposition was associated with histologic injury [ 98 ]. FHR-5 co-localized and correlated with IgA as well as C3 deposits.…”

“…These data indicate that FHR-5 might be a key contributor to complement dysregulation in IgAN ( Table 1 ). It is important to mention that FHR-5 detection by immunohistochemistry in the study by Medjeral-Thomas et al and by Guo et al was achieved by using rabbit polyclonal antibodies against FHR-5 [ 88 , 98 ], creating the possibility of cross-reactivity with other FHRs [ 37 ].…”