In utero sensitization modulates IgG isotype, IFN-c and IL-10 responses of neonates in bancroftian filariasis K. G. ACHARY, 1 N. N. MANDAL, 1 S. MISHRA, 1 R. MISHRA, 1 S. S. SARANGI, 2 A. K. SATAPATHY, 1 S. K. KAR 1 & M. S. BAL 1 1 Division of Immunology, Regional Medical Research Center (Indian Council of Medical Research), Bhubaneswar, Odisha, India, 2 Government Hospital, Khurda, Odisha, India SUMMARY In utero exposure has been considered as a risk factor for filarial infection. To evaluate the influence of maternal infec- tion on filarial-specific IgG subclass response in neonates and their correlation with plasma levels IL-10 and inter- feron-c, 145 pairs of mothers and their respective cord bloods were examined. Transplacental transfer of circulating filarial antigen (CFA) was observed in 34Á8% cord bloods from CFA positive mothers. Filarial-specific IgG1, IgG2 and IgG4 responses of cord bloods were found to be positively correlated with CFA of mothers. In contrast, IgG3 responses negatively correlated with CFA of mothers. The % of simi- larity of recognition pattern in the cord blood with maternal blood was high for IgG3 response than IgG4 in all three groups. An increased levels of IL-10 and decreased levels of interferon gamma (IFN-c) were observed in cord blood of infected mothers. Interferon gamma was positively correlated with IgG3 and negatively correlated with IgG4 level. On the other hand, IL-10 was positively correlated with IgG4 and CFA, indicating that cytokines may play a role in modulat- ing the immune responses in cord bloods of sensitized foetus. The findings of the study reveal that in utero tolerance or sensitization may influence the filarial-specific immunity to infection in neonates. Keywords circulating filarial antigen, filariasis, IgG3, IgG4, interferon gamma, maternal filarial infection INTRODUCTION Lymphatic filariasis (LF) is an important public health problem endemic in 73 countries including India. It is a major cause of acute and chronic morbidity and a signifi- cant impediment to socio-economic development in all endemic areas (1). About 22 million children below 15 years of age are infected with filariasis, which is around 17% of the total disease burden, (2) but till now there are no reports available for infant infections. Lot of evidence exist suggesting that infection is acquired in earlier child- hood and the clinical manifestations appear much later (3–5). The mechanism behind this various manifestation could be due to host, environmental or maternal infection. The earliest potential exposure of the human host to filari- al antigens is in the uterine environment. In utero exposure of the developing foetus to filarial antigens causes altered immunity of the children, making a long-term hyporespon- siveness to filarial antigen (6). Children whose mothers were microfilaraemic during gestation were more likely to be microfilaraemic compared with children whose mothers were amicrofilaraemic during gestation (7–9). In utero sensitization to Ascaris lumbricoides was also reported in newborns with ascariasis (10). During pregnancy, parasite- specific antibodies and antigens may cross transplacental barrier from mother to their foetus and evidence exist that prenatal sensitization to filarial antigen occurs in human filariasis and that children born from infected mothers are at increased risk of infection compared with offspring of uninfected mothers (11, 12). In last decade, several studies have been carried out to know the effect of prenatal sensi- tization on neonatal immune responses. Several evidence suggested that helminth infections cause immunological disorders by provoking the immune system towards Th2 with overproduction of Th2 cytokines and IgG4, and IgE immunoglobulin subclasses (13, 14). Therefore, study of antibody as well as T cell responses with cytokine profile is essential to understand the nature Correspondence: M. S. Bal, Division of Immunology, Regional Medical Research Centre (Indian council of Medical Research), Chandrasekharpur, Bhubaneswar – 751023 Odisha, India (e-mail: balmadhusmita@gmail.com). Received: 14 June 2013 Accepted for publication: 31 May 2014 © 2014 John Wiley & Sons Ltd 485 Parasite Immunology, 2014, 36, 485–493 DOI: 10.1111/pim.12121