In patients treated with Privigen or dexamethasone, the C6 Lyme index did not increase or only marginally increased, with none reaching the cutoff. index increased in 95% (40/42) of patients treated with Nanogam (Physique?1), reaching the cutoff (Lyme index 0.90) in 51% (20/39) of previously seronegative patients. In patients treated with Privigen or dexamethasone, the C6 Lyme index did not increase or only marginally increased, with none reaching the cutoff. Rabbit Polyclonal to PYK2 One Privigen\treated patient already experienced a positive C6 Lyme index before and during IVIg, without immunoblot confirmation, and was therefore considered seronegative. Open in a YF-2 separate window Physique 1 Quantitative C6 Lyme index in patients treated with intravenous immunoglobulin (IVIg) or dexamethasone. (a) Patients treated with Nanogam?. (b) Patients treated with Privigen?. (c) Patients treated with dexamethasone. Cutoff values recommended by the manufacturer are depicted by the dotted lines; C6 Lyme index 0.90 is considered a negative result, 0.90C1.09 an equivocal result and 1.10 a positive result [Colour figure can be viewed at wileyonlinelibrary.com] One Nanogam\treated patient had also apparent seroconversion for IgM antibodies during IVIg. This patient experienced a negative C6 Lyme index pre\treatment; an additionally performed immunoblot was equivocal for IgM and unfavorable for IgG. The follow\up sample of this individual was C6, IgM and IgG negative. Follow\up samples post\treatment were available for 13 patients with apparent seroconversion. Median treatment duration was 4 (range 4C12) months. Twelve patients (92%) showed seroreversion. An early follow\up sample (1C3?months) after withdrawal of IVIg was available in nine patients; seven patients (78%) experienced seroreversion and two patients experienced an equivocal C6 Lyme index. Of these two patients, one experienced unfavorable IgM and IgG immunoblots and the C6 Lyme index 8?months after withdrawal was negative. In the second patient the IgG immunoblot was positive and no further follow\up samples were available. In later follow\up samples no equivocal or positive C6 Lyme indexes were found. The C6 Lyme index in these patients pre\, during and post\IVIg are shown in Physique S1 , Direct screening of IVIg showed a positive C6 Lyme index (3.25) for Nanogam and a negative C6\index (0.50) for Privigen. The immunoblot performed on Nanogam was highly positive for anti\Bbsl IgG antibodies and unfavorable for IgM. DISCUSSION In this study we observed apparent seroconversion for anti\Bbsl antibodies in 48% of patients treated with Nanogam. None of the patients treated with Privigen or dexamethasone showed apparent seroconversion. Interestingly, antibodies disappeared in 92% of patients during follow\up after IVIg withdrawal. We found an anti\Bbsl antibody seroprevalence of 3%, comparable with the Dutch populace (4%C8%) [7]. However, the prevalence of anti\Bbsl antibodies depends on geographical region [8], possibly explaining the difference in YF-2 apparent seroconversion between patients receiving Nanogam, a Dutch product, and Privigen, produced in either the USA or Germany. The finding that the C6 Lyme index was positive in Nanogam and unfavorable in Privigen, is usually in accordance with previous findings [3]. Interestingly, one patient experienced apparent seroconversion for both IgM and IgG antibodies during IVIg treatment (Nanogam). IVIg consists of at least 95% of IgG antibodies, and a very small proportion of YF-2 IgA antibodies (CSL Behring prescribing information on Privigen; Sanquin product information on Nanogam). We cannot exclude the presence of a minimal portion of IgM, although anti\Bbsl IgM antibodies were not exhibited in the Nanogam batch we tested. Alternatively, the obtaining in this particular patient that both IgM and IgG were unfavorable during follow\up, without antibiotic treatment, makes Lyme borreliosis unlikely. All but one patient with IVIg\induced apparent seroconversion returned to a seronegative state within a few months post\treatment. In this patient, anti\Bbsl IgG antibodies were still detectable by immunoblot 8 weeks post\treatment. This could most likely be YF-2 explained by the finding that IVIg metabolism differs greatly between patients, with a half\life ranging between 18 and 32?days [9]. Regrettably, no later follow\up samples were available for this patient. Alternatively, albeit less likely, this could have reflected interim exposure to Bbsl. The strengths of this study include the relatively large sample size. Samples from at least two time points were available for all patients and two different types of IVIg were used. A limitation is that not all follow\up samples were taken at the same time point. Therefore, we are not able to calculate when serological screening for Lyme borreliosis would be reliable again after IVIg treatment. Regrettably, we did not test different batches of Nanogam to see if apparent seroconversion was batch\related. The batch numbers of the Nanogam the patients were treated with were.