ループス腎炎の診断の進展(Advancing Diagnostics for Lupus Nephritis)

2022-05-05

タンパク質の大規模な検査でバイオマーカーの可能性を発見 Large Scale Protein Exam Leads to Potential Biomarkers
1. イムノプロテオミクスによるループス腎炎における新規循環型免疫複合体の発見 Discovery of Novel Circulating Immune Complexes in Lupus Nephritis Using Immunoproteomics
  1. Abstract

タンパク質の大規模な検査でバイオマーカーの可能性を発見 Large Scale Protein Exam Leads to Potential Biomarkers

2022-05-04 ヒューストン大学(UH)

腎臓の炎症であり、ループス患者の主要な死亡原因であるループス腎炎(LN)の典型的な臨床検査の性質は、困難さに満ちています。侵襲的な腎生検は痛みを伴い、腎臓に損傷を与える可能性があります。残念ながら、しばしば障害をもたらす自己免疫疾患である全身性エリテマトーデス(SLE)患者の60%は、致命的となりうるループス腎炎に進むと、この負担に直面することになるのです。
ヒューストン大学生体工学部准教授のTianfu Wuは、「SLE/LN患者の精密診断と個別化治療のための分類における異質性とアンメットニーズを考えると、新規バイオマーカー、特にバイオマーカーパネルの特定が最も重要です」と、雑誌「Frontiers in Immunology」で報告しています。

<関連情報>

イムノプロテオミクスによるループス腎炎における新規循環型免疫複合体の発見 Discovery of Novel Circulating Immune Complexes in Lupus Nephritis Using Immunoproteomics

Chenling Tang, Min Fang, Gongjun Tan, Shu Zhang, Bowen Yang, Yaxi Li, Ting Zhang, Ramesh Saxena, Chandra Mohan and Tianfu Wu
Frontiers in Immunology Published:24 March 2022
DOI:https://doi.org/10.3389/fimmu.2022.850015

Abstract

Objective: The goal is to discover novel circulating immune complexes (ICx) in the serum of lupus nephritis (LN) as potential biomarkers.

Methods: Protein A/G magnetic beads or C1q-coated plates were used to capture ICx in the serum of LN, followed by the identification of immunoglobulin-binding proteins using liquid chromatography and tandem mass spectrometry (LC-MS/MS). Bioinformatic approaches and single-cell RNA sequencing (scRNA Seq) databases were used to select potential candidate ICx markers in LN. The selected ICx markers were further validated using ELISA.

Results: A total of 300 immunoglobulin-binding proteins were discovered in the screening, among which 77 proteins were detectable only in LN samples. Bioinformatics-assisted selection allowed us to further identify 10 potential immunoglobulin-binding proteins, which form ICx as potential biomarkers in LN. In a validation cohort of 62 LN patients and 21 healthy controls (HC), we found that prolyl 3-hydroxylase 1 (P3H1), phosphatase and actin regulator 4 (PHACTR4), and regulator of G-protein signaling 12 (RGS12) ICx exhibited discriminative capability in distinguishing LN from HC, with an area under the curve (AUC) values of 0.82, 0.99, and 0.90, respectively. Furthermore, a biomarker panel comprising CD14, CD34, cystatin A, myocyte enhancer factor 2C (MEF2C), RGS12, and ubiquitin C (UBC) ICx could distinguish active LN from inactive LN with an AUC value of 0.85, which is comparable to or better than pathological parameters such as renal activity index (AI) and renal chronicity index (CI).

Conclusion: Immunoproteomics-based discovery studies have enabled us to identify circulating immune complexes as potential biomarkers of LN.