Identification of Novel, Immunogenic HLA-DR-Presented Prevotella copri Peptides in Patients With Rheumatoid Arthritis.
Identification of Novel, Immunogenic HLA-DR-Presented Prevotella copri Peptides in Patients With Rheumatoid Arthritis.
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DOI：
10.1002/art.41807
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Steere AC
中科院分区：
文献类型：
--
作者：
Pianta A;Chiumento G;Ramsden K;Wang Q;Strle K;Arvikar S;Costello CE;Steere AC
我们以前确定了HLA-DR提出的表位从一个RA患者的PBMC中获得的普雷沃氏菌copri（Pc）的27 kD蛋白。在此，我们试图从其他患者的PBMC中鉴定其他HLA-DR呈递的Pc肽和源蛋白，以更好地了解Pc免疫反应和RA疾病发病机制。利用串联质谱法，我们搜索了RA和莱姆关节炎（LA）患者PBMC中HLA-DR呈递的Pc肽。在RA患者、患有其他关节炎的患者或一般人群中测试所鉴定的肽和源蛋白的反应性;结果与临床发现相关。包括Pc-p27，我们已经确定了5个HLA-DR提出的Pc肽，每个来自不同的Pc蛋白，在3的4例RA患者，但没有在2例LA患者。在我们的RA队列中进行检测时，19例患者中有14例（74%）具有T细胞应答，89例患者中有47例（53%）具有IgG或伊加应答，其中5种Pc肽或蛋白质中有≥1种，最常见的伊加与Pc-p27反应。此外，74%的伊加抗体≥1 Pc蛋白的RA患者有抗瓜氨酸蛋白抗体（ACPA），而缺乏伊加Pc抗体应答的患者有49%（P=0.05），伊加Pc抗体水平与ACPA值相关。我们的大多数RA患者具有Pc免疫应答。伊加Pc抗体，特别是Pc-p27，与ACPA的相关性支持粘膜中的特异性微生物抗原在RA关节中形成或放大免疫应答中起作用的假设。
We previously identified HLA-DR-presented epitopes from a 27-kD protein of Prevotella copri (Pc) obtained from the PBMC of one RA patient. Herein, we sought to identify other HLA-DR-presented Pc peptides and source proteins from the PBMC of additional patients to better understand Pc immune responses and RA disease pathogenesis. Using tandem mass spectrometry, we searched for HLA-DR-presented Pc peptides in PBMC from RA and Lyme arthritis (LA) patients. The identified peptides and source proteins were tested for reactivity in RA patients, those with other arthritides, or the general population; the results were correlated with clinical findings. Including Pc-p27, we have identified 5 HLA-DR-presented Pc peptides, each derived from a different Pc protein, in 3 of 4 RA patients, but none in 2 LA patients. When tested in our RA cohort, 14 of 19 patients (74%) had T cell responses and 47 of 89 patients (53%) had IgG or IgA responses with ≥1 of the 5 Pc peptides or proteins, most commonly IgA reactivity with Pc-p27. Additionally, 74% of RA patients with IgA antibodies to ≥1 Pc protein had anti-citrullinated protein antibodies (ACPA) compared with 49% of patients who lacked IgA Pc antibody responses (P=0.05), and IgA Pc antibody levels correlated with ACPA values. The majority of our RA patients had Pc immune responses. The correlation of IgA Pc antibodies, particularly to Pc-p27, with ACPA supports the hypothesis that specific microbial antigens in the mucosa have a role in shaping or amplifying immune responses in RA joints.
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影响因子：
30.3
作者：
Rubinstein MR;Wang X;Liu W;Hao Y;Cai G;Han YW
通讯作者：
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影响因子：
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作者：
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作者：
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作者：
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通讯作者：
Bykerk, Vivian
DOI：
10.1126/science.aar7201
发表时间：
2018-03-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Manfredo Vieira S;Hiltensperger M;Kumar V;Zegarra-Ruiz D;Dehner C;Khan N;Costa FRC;Tiniakou E;Greiling T;Ruff W;Barbieri A;Kriegel C;Mehta SS;Knight JR;Jain D;Goodman AL;Kriegel MA
通讯作者：
Kriegel MA