Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Biochemistry, Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, Massachusetts.
Arthritis Rheumatol. 2023 Jul;75(7):1263-1274. doi: 10.1002/art.42465. Epub 2023 May 11.
Terminal glycans on the Fc portion of IgG antibodies are critical for antibody-triggered, proinflammatory or antiinflammatory responses. We undertook this study to compare glycan profiles of total IgG1 and Borrelia burgdorferi (Bb)-specific IgG1 antibodies in patients with oral antibiotic-responsive or antibiotic-refractory Lyme arthritis (LA).
Following affinity-column processing, glycan profiles of IgG antibodies were determined in serum and synovial fluid (SF) samples of 21 LA patients using glycoblotting with hydrazide glycan enrichment and determination of glycan structure by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Correlations between glycan profiles and treatment outcomes were analyzed.
Compared with patients with antibiotic-refractory LA, those with antibiotic-responsive LA had total and Bb-specific IgG1 antibody glycans with less intense inflammatory profiles, containing lower percentages of N-acetylglucosamine (GlcNAc) and bisecting GlcNAc and higher percentages of galactose and fucose. In contrast, patients with antibiotic-refractory LA prior to receiving IV antibiotic therapy had total IgG1 and Bb IgG1 antibodies with maximal, minimally opposed, proinflammatory glycan profiles, containing high percentages of GlcNAc and bisecting GlcNAc, intermediate percentages with galactose and fucose, and low percentages with N-acetylneuraminic acid (sialic acid). Patients with refractory LA who were first seen with synovitis after receiving IV antibiotic therapy still had Bb IgG1 antibodies with strongly inflammatory glycan profiles, but their inflammatory potential appeared to be waning.
Patients with oral antibiotic-responsive LA had Bb IgG1 antibodies with more balanced proinflammatory/antiinflammatory glycan profiles, whereas patients with antibiotic-refractory LA had Bb IgG1 antibodies with maximal, minimally opposed, proinflammatory glycan profiles. Among patients with antibiotic-refractory LA, antibodies with this unbalanced inflammatory glycan profile may have a role in sustaining maladaptive joint inflammation.
IgG 抗体 Fc 部分的末端糖基对于抗体触发的促炎或抗炎反应至关重要。我们进行这项研究是为了比较口服抗生素反应性或抗生素难治性莱姆关节炎（LA）患者血清和滑液（SF）中总 IgG1 和伯氏疏螺旋体（Bb）特异性 IgG1 抗体的聚糖谱。
在亲和柱处理后，通过肼基糖富集的糖基印迹和基质辅助激光解吸电离飞行时间质谱测定糖结构，在 21 例 LA 患者的血清和 SF 样本中测定 IgG 抗体的聚糖谱。分析聚糖谱与治疗结果之间的相关性。
与抗生素难治性 LA 患者相比，抗生素反应性 LA 患者的总 IgG1 和 Bb 特异性 IgG1 抗体聚糖具有较低的炎症特征，其 N-乙酰葡萄糖胺（GlcNAc）和双分支 GlcNAc的百分比较低，而半乳糖和岩藻糖的百分比较高。相比之下，在接受 IV 抗生素治疗之前，抗生素难治性 LA 患者的总 IgG1 和 Bb IgG1 抗体具有最大、最小拮抗的促炎聚糖谱，含有高百分比的 GlcNAc 和双分支 GlcNAc，中等百分比的半乳糖和岩藻糖，以及低百分比的 N-乙酰神经氨酸（唾液酸）。在接受 IV 抗生素治疗后出现滑膜炎的首次就诊的难治性 LA 患者仍具有强烈炎症性聚糖谱的 Bb IgG1 抗体，但它们的炎症潜力似乎正在减弱。
口服抗生素反应性 LA 患者的 Bb IgG1 抗体具有更平衡的促炎/抗炎聚糖谱，而抗生素难治性 LA 患者的 Bb IgG1 抗体具有最大、最小拮抗的促炎聚糖谱。在抗生素难治性 LA 患者中，具有这种不平衡炎症性聚糖谱的抗体可能在维持适应性关节炎症中发挥作用。
