Long-term persistence of specific T- and B-lymphocyte responses to Borrelia burgdorferi following untreated neuroborreliosis

Abstract

Follow-up studies on 56 patients who suffered from antibiotically untreated, acute, monophasic neuroborreliosis five to 23 years ago revealed significant positive levels of IgG antibodies to Borrelia burgdorferi (Bb) in the serum and cerebrospinal fluid (CSF) of 20 patients (IFT, ELISA, Bb-specific IgG Western blot, Bb-specific IEF-IgG immunoblot). Nine of 10 tested patients had a definitely positive T-cell proliferative response to whole B. burgdorferi, with a mean (+/- -SEM) stimulation index of 7.2 +/- 1.8. Because the patients studied exhibited no, or only mild to medium sequelae without any evidence of a chronic-progressive disease, we interpret the long-term persistence of specific T- and B-lymphocyte responses to B. burgdorferi as an "immunological scar syndrome". Finally, diagnostic criteria of active neuroborreliosis are proposed.

EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis

“…Activation of patient‐derived lymphocytes is measured after incubation with Borrelia antigens. Results of studies are contradictory; moreover, there is no relevant study that allows assessment of diagnostic sensitivity and specificity of the tests that are promulgated for diagnosis of Lyme borreliosis [68–72].…”

Unconventional diagnostic tests for Lyme borreliosis: a systematic review

“…Among 38 publications identified through database searches, 24 were screened, after removing duplicates, and 14 full texts were assessed for eligibility. Ten studies were finally retained for the review: eight prospective controlled studies [54e61], one prospective uncontrolled study [62] and one retrospective controlled study [63]. QUADAS-2 quality assessment demonstrated low risk of bias and uncertainty regarding applicability for two prospective controlled studies [54,61], unclear risk of bias and uncertainty regarding applicability for six prospective studies [55e60], and high risk of bias and high applicability concerns for the two others [62,63].…”

“…Among the ten studies retained, for early LB, mean SIs were >10 in two [60,61], <10 in one [58] and not mentioned in seven [54e57, 59,62,63]; whereas for late LB, mean SIs were >10 in five [54,55,57,60,61], <10 in two [58,63] and not mentioned in three [56,59,62]. For controls (healthy participants or other diseases), mean SIs were <10 in five studies [54,55,57,58,63], >10 in one [61], and not mentioned in four [56,59,60,62]. Exposed healthy participants (forest workers, Borrelia laboratory workers) had high seroprevalence, with mean SI >10 in one report, <10 in two [54,59] and not given in seven [55e58,61e63].…”

“…Concordance with serological tests was found in four studies, two each performed on late LB or at all stages [55,57,60,63], and discordance in the six others conducted at all stages combined [54,56,58,59,61,62].…”

“…Second, LB was defined with criteria other than those of ESGBOR or IDSA in six [4,54e56,58,59,62]. Third, the international SI cut-off to interpret results was not respected in four [59,60,62,63] and not mentioned in five [55e58,61], meaning that nine studies do not enable any conclusion to be drawn. Finally, the numbers of patients with SI >10 were not given in six studies [55e57,59,62,63] that reported only mean SIs.…”