Analysis Of The Clinicopathological Features Of Light Chain Amyloid Cast Nephropathy And The Protein Expression Profile Of Local Renal Tissues

Objective:Light chain amyloid casts(LCAC),including isolated light chain amyloid casts(I-LCAC),and light chain amyloid casts with light chain amyloid nephropathy(LCAC&AL),which are rare diseases,the existing literature is primarily concentrated in case reports,and there is still a lack of research on case cohorts.Little is known about the disease’s incidence,pathology,and clinical significance.There is also a lack of specific protein markers for differential diagnosis,which is very easy to cause missed diagnosis And misdiagnosis,causing severe consequences to the life and health of patients.In this study,a retrospective case-control study was conducted to explore the incidence of the disease and its clinicopathological relationship and,simultaneously,explore protein markers in patients with LCAC nephropathy to assist in the accurate diagnosis and differential diagnosis of the disease.Lay the foundation for more precise treatment of patients.Methods:This study divided LCAC cases into isolated light chain amyloid casts(I-LCAC)group and LCAC combined with light chain amyloid nephropathy(LCAC&AL)group.Light microscopy,immunofluorescence,electron microscopy,and immunoelectron microscopy were used to analyze the pathological examinations of the two groups of patients with semi-quantitative scores and to evaluate the clinicopathological characteristics of the two groups of patients.The cases of the I-LCAC nephropathy group and light chain cast nephropathy(LCCN)group were analyzed by laser microdissection combined with mass spectrometry to identify the differentially expressed proteins in the histology of the two groups of patients and through biological information analysis Screen differentially expressed proteins and find out candidate protein markers after reviewing the literature.Results:From January 2018 to June 2021,Guangzhou KingMed Medical Laboratory Center diagnosed 131 patients with light chain cast nephropathy(LCCN),of which 15 cases were diagnosed as LCAC(11.5%),including 10 points in the I-LCAC group and There were 5 cases in the LCAC&AL group;9 patients in LCAC were clinically diagnosed with multiple myeloma,including 7 cases in the I-LCAC group and 2 cases in the LCAC&AL group,and there was no statistically significant difference between the two groups;compared with the LCAC&AL group,blood The creatinine level(766.1 μmol/L vs 82.8μmol/L)and the proportion of anemia(100%vs 40%)were higher(P<0.05).The average number of starch casts per square millimeter in the I-LCAC group(7.3 vs 0.3)was significantly more than that in the LCAC&AL group(P<0.05),and the light chain type of the casts mainly was the X type;The average number of amyloid casts was positively correlated with the patient’s serum creatinine level(R2=0.593).889 proteins were identified in the mass spectrometry results of 13 tissue samples(9 samples from the I-LCAC group and 4 samples from the LCCN group),of which 37 were differential proteins.Patients in the I-LCAC group were compared with those in the LCCN group.There are 27 up-regulated proteins and 10 down-regulated proteins.Based on the bioinformatics analysis results and the differential protein information table,the up-regulated differential proteins with a higher expression ratio(LCAC/LCCN ratio)in the LCAC group and the LCCN group were selected,combined with the literature,and finally,the neutrophil gelatinase-associated lipocalin(NGAL),matrix metalloproteinase 9(MMP-9),serum amyloid P-component(SAP)can be used as potential candidate protein markers.Conclusions:The most common etiology of LCAC is multiple myeloma,which has unique pathological morphological characteristics and staining characteristics.Compared with the LCAC&AL group,patients with I-LCAC pathological type are more prone to renal function damage.The more the average number of starch casts per square millimeter,the worse the renal function.The diagnosis of the disease needs to rely on immunopathological examination.NGAL,MMP-9,and SAP may be regulatory proteins in LCAC nephropathy’s pathogenesis,becoming potential protein markers of LCAC nephropathy.