Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy.

Soares, Maria F; Genitsch Gratwohl, Vera; Chakera, Aron; Smith, Andrew; MacEwen, Clare; Bellur, Shubha S; Alham, Nasullah K; Roberts, Ian S D (2019). Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy. Histopathology, 74(4), pp. 629-637. Wiley-Blackwell 10.1111/his.13768

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AIMS The Oxford Classification E score (endocapillary hypercellularity) predicts renal functional decline in IgA nephropathy (IgAN) patients free from steroid/immunosuppressive (IS) therapy, but is poorly reproducible. We hypothesise that endocapillary hypercellularity reflects glomerular inflammation and that the presence of CD68-positive cells is a more robust marker of E score. METHODS AND RESULTS CD68-positive cells were quantified in glomeruli and tubulointerstitium in biopsies from 118 IgAN patients, and cell counts were correlated with the criteria of the Oxford Classification, assigned on PAS-stained serial sections. There was a strong correlation between median glomerular CD68 count and the percentage of glomeruli showing endocapillary hypercellularity (r = 0.67; P < 0.001; r2  = 0.45), while there was no correlation between CD68-positive cells and mesangial hypercellularity, % segmental sclerosis, % of crescents and % tubular atrophy/interstitial fibrosis (TA/IF). ROC curve analysis demonstrated that a maximum glomerular CD68 count of 6 is the best cut-off for distinguishing E0 from E1 (sensitivity 94.1%, specificity 71%, area under the curve = 89%). Identification of biopsies with a maximum glomerular CD68-count >6 was reproducible (kappa score 0.8), and there was a strong correlation between glomerular CD68 counts obtained by conventional light microscopy and by image analysis (r = 0.80, r2  = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68-positive cells correlated moderately with % TA/IF (r = 0.59, r2  = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r2  = 0.29, P < 0.0001), but not with mesangial and endocapillary hypercellularity. CONCLUSIONS While glomerular CD68-positive cells emerge as markers of endocapillary hypercellularity, their tubulointerstitial counterparts are associated with chronic damage.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Genitsch Gratwohl, Vera

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0309-0167

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Vera Genitsch Gratwohl

Date Deposited:

13 Nov 2019 12:27

Last Modified:

13 Nov 2019 14:01

Publisher DOI:

10.1111/his.13768

PubMed ID:

30303541

Uncontrolled Keywords:

IgA nephropathy glomerulonephritis macrophages

BORIS DOI:

10.7892/boris.134695

URI:

https://boris.unibe.ch/id/eprint/134695

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