Heightened Proinflammatory Glycosylation of Borrelia burgdorferi IgG Antibodies in Synovial Fluid in Patients With Antibiotic-Refractory Lyme Arthritis.
Heightened Proinflammatory Glycosylation of Borrelia burgdorferi IgG Antibodies in Synovial Fluid in Patients With Antibiotic-Refractory Lyme Arthritis.
复制标题
抗生素难治性莱姆关节炎患者滑液中伯氏疏螺旋体 IgG 抗体的促炎糖基化增强。
DOI：
10.1002/art.42465
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Steere,AllenC
中科院分区：
文献类型：
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作者：
Sanes,JurgenT;Costello,CatherineE;Steere,AllenC
目的Ig G抗体Fc段末端的糖链在抗体触发、促炎或抗炎反应中起关键作用。本研究比较了口服抗生素敏感或抗生素耐药的莱姆关节炎(LA)患者血清中总IgG1和伯氏疏螺旋体(BB)特异性IgG1抗体的糖链图谱。方法采用亲和层析-柱层析方法，采用糖印迹-肼聚糖富集技术和基质辅助激光解吸电离飞行时间质谱仪测定了21例LA患者血清和滑液中的IgG抗体的糖链图谱。结果与抗生素耐药的LA患者相比，抗生素敏感的LA患者总的和BB特异性的IgG1抗体糖链的炎症特征较轻，其中N-乙酰氨基葡萄糖(GlcNAc)和对分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，在接受静脉抗生素治疗之前，抗生素难治性LA患者的总IgG1和BB IgG1抗体具有最大、最小相反的促炎糖谱，包含高百分比的GlcNAc和一分为二的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)。难治性LA患者在接受静脉抗生素治疗后首次发现滑膜炎，其BB IgG1抗体仍具有强烈的炎症糖链图谱，但其炎症潜能似乎正在减弱。结论口服抗生素敏感的LA患者的BB IgG1抗体具有更平衡的促炎/抗炎糖谱，而抗生素难治性LA患者的BB IgG1抗体具有最大的、最小相反的促炎症糖链图谱。在抗生素耐药的LA患者中，具有这种不平衡的炎性糖链的抗体可能在维持不适应性关节炎症中起作用。
ObjectiveTerminal 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 andBorrelia burgdorferi(Bb)–specific IgG1 antibodies in patients with oral antibiotic–responsive or antibiotic‐refractory Lyme arthritis (LA).MethodsFollowing 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.ResultsCompared 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 ofN‐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 withN‐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.ConclusionPatients 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.