Fung B P, McHugh G L, Leong J M, Steere A C
Division of Rheumatology/Immunology, New England Medical Center, Boston, Massachusetts 02111.
Infect Immun. 1994 Aug;62(8):3213-21. doi: 10.1128/iai.62.8.3213-3221.1994.
We determined the humoral immune response to outer surface protein C (OspC) of Borrelia burgdorferi in patients with early or late manifestations of Lyme disease and investigated the use of this antigen in the serodiagnosis of early infection. The ospC gene from the low-passage human isolate 297, a North American B. burgdorferi strain, was used to make a recombinant maltose-binding protein (MBP)-OspC fusion protein for serologic tests. This gene showed 84 to 85% nucleotide sequence identity and 76 to 79% amino acid identity with ospC of B. burgdorferi B31 and 2591. The antibody responses to MBP-OspC were determined in serial sera from 15 patients with Lyme disease who were monitored for 4 to 12 years of illness, in single-serum samples from 189 patients with early or late manifestations of the disorder, and in serum samples from 106 control patients. Early in the infection, patients with erythema migrans or meningitis commonly had weak to strong immunoglobulin M (IgM) responses to OspC and sometimes weak to moderate IgG responses. Months to years later, weak to strong IgG reactivity with this protein was often apparent in patients with arthritis, but this response was weak or absent in patients with chronic neuroborreliosis. When acute- and convalescent-phase serum samples from patients with erythema migrans were tested for reactivity against MBP-OspC, the sensitivity of the IgM test was 73% and the specificity was 98%, with either enzyme-linked immunosorbent assay (ELISA) or Western blotting. We conclude that the majority of patients with Lyme disease have a prominent IgM response to OspC early in the illness, which is often followed by a prominent IgG response in patients with arthritis. For the serodiagnosis of early infection, the sensitivity and specificity of IgM ELISA and Western blotting were comparable or slightly improved when MBP-OspC was used as the antigen compared with tests in which spirochetal lysates were used.
我们测定了莱姆病早期或晚期患者对伯氏疏螺旋体外表面蛋白C（OspC）的体液免疫反应，并研究了该抗原在早期感染血清诊断中的应用。来自低传代人分离株297（一种北美伯氏疏螺旋体菌株）的ospC基因用于制备重组麦芽糖结合蛋白（MBP）-OspC融合蛋白用于血清学检测。该基因与伯氏疏螺旋体B31和2591的ospC具有84%至85%的核苷酸序列同一性以及76%至79%的氨基酸同一性。在15例随访4至12年的莱姆病患者的系列血清、189例该疾病早期或晚期表现患者的单份血清样本以及106例对照患者的血清样本中测定了对MBP-OspC的抗体反应。在感染早期，游走性红斑或脑膜炎患者通常对OspC有弱至强的免疫球蛋白M（IgM）反应，有时对IgG有弱至中度反应。数月至数年之后，关节炎患者通常对该蛋白有弱至强的IgG反应，但慢性神经伯氏疏螺旋体病患者的这种反应较弱或不存在。当检测游走性红斑患者急性期和恢复期血清样本对MBP-OspC的反应性时，无论是采用酶联免疫吸附测定（ELISA）还是免疫印迹法，IgM检测的敏感性均为73%，特异性为98%。我们得出结论，大多数莱姆病患者在疾病早期对OspC有显著的IgM反应，随后关节炎患者通常会出现显著的IgG反应。对于早期感染的血清诊断，与使用螺旋体裂解物进行检测相比，以MBP-OspC作为抗原时，IgM ELISA和免疫印迹法的敏感性和特异性相当或略有提高。
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