THU0378 Wire-loop lesion is associated with serological immune abnormality, but not renal prognosis in lupus nephritis
Authors: T. Zoshima, S. Hara, M. Kawano
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Classification of Lupus Nephritis (LN) defines wire-loop lesion (WL) as an active lesion (AL). In it, LN patients with WL are classified as class III or IV, which are associated with a poor prognosis and recommended to be treated by intense immunosuppressive therapy including corticosteroid, cyclophosphamide, mycophenolate mofetil and other immunosuppressants.<sup><sup>1</sup></sup> However, among AL, few reports have focused on the clinicopathological impact of WL on serological immune abnormality and renal prognosis. <h3>Objectives</h3> To identify clinicopathological characteristics associated with WL, and to clarify whether WL predicts renal prognosis of LN. <h3>Methods</h3> We enrolled 117 Japanese LN patients subjected to renal biopsy in 11 hospitals from 2000 to 2017. We measured clinical findings at the time of renal biopsy, including creatinine (Cr), estimated glomerular filtration rate (eGFR), total protein (TP), IgG, IgA, IgM, C3, C4, CH50, anti-nuclear antibodies (Abs), anti-double strand DNA (dsDNA) Abs, anti-Sm Abs, anti-RNP Abs in the sera, urinalysis, and presence of comorbidities (antiphospholipid antibody syndrome, hypertension, hyperlipidemia, diabetes mellitus, and hyperuricemia). Renal biopsy findings were classified by ISN/RPS classification including AL and chronic lesions (CL). Immune deposit was evaluated by immunofluorescence. We also measured Cr and eGFR at the last patient visit, and recorded medications prescribed for LN. Chronic kidney disease (CKD) was defined as eGFR &lt;60 ml/min/1.73 m2. In class III or IV patients, we retrospectively compared these clinical and histological findings between those with WL (WL +group) and without WL (WL- group). <h3>Results</h3> Of 117 patients, 94 (81.2%) were classified as class III or IV (78 females; mean age 41.3 years; observational period 5.8±5.2 years). WL was found in 27 of them (28.7%). Although there was no significant difference in renal function (eGFR; 81.1±31.4 vs 80.6±34.4 ml/min/1.73 m2, p=0.91), WL +group had higher titer of serum anti-dsDNA Abs (median values; 205 vs 67 IU/ml, p=0.011) and lower level of TP (5.7±1.2 vs 6.3±1.0 g/dl, p=0.025) than WL- group. There were no significant differences in any other clinical findings. In histological findings, most WL (96.3%) were accompanied by other ALs such as endocapillary proliferation and/or crescent formation. WL +group had a higher frequency of class IV, AL and IgM deposit, while CL did not differ between the two groups. Linear regression analysis revealed associations between anti-dsDNA Abs and IgM deposit and WL (β=0.48, p&lt;0.01; β=0.26, p=0.016, respectively). There was no difference in the latest renal function (eGFR; 76.9±27.5 vs 74.0±29.5 ml/min/1.73 m2, p=0.72) between the two groups. Cox regression analysis revealed significant associations between AL such as necrosis, CL, initial eGFR, HT, HL and medication for LN with CKD at the last visit, but not with WL (p=0.13). <h3>Conclusions</h3> WL was associated with serum anti-dsDNA Abs, but not with renal prognosis, suggesting that WL reflects immune abnormality, but is not an independent factor predictive of the renal prognosis of LN. Although WL is defined as an AL in the present classification, this may need to be revised to better reflect its clinical impact. <h3>Reference</h3> [1] Ann Rheum Dis2012;71:1771–82. <h3>Disclosure of Interest</h3> None declared