IgG4-related disease (IgG4-RD) is a rare and often misdiagnosed disorder with limited literature that highlights the different neurological presentations of this treatable disease. The diagnosis of IgG4-RD could be challenging, while imaging is fundamental for the diagnosis, biopsy is considered the gold standard. Most cases respond well to steroids and immunosuppressive therapy. This is a case series study that illustrates the varied neurological presentations of IgG4-RD through three different patients that were followed at the Montreal Neurological Institute. This paper takes you through the diagnostic strategy that we followed to accurately diagnose and treat those patients.

To improve the diagnosis of human fascioliasis caused by Fasciola gigantica, we developed a peptide-based enzyme-linked immunosorbent assay (peptide-based ELISA) based on the detection of specific IgG4 subclass antibody. Two identified B-cell epitopes of F. gigantica cathepsin L1 were synthesized as single synthetic peptides, acetyl-DKIDWRESGYVTELKDQGNC-carboxamide (peptide L) and acetyl-DKIDWRESGYVTEVKDQGNC-carboxamide (peptide V), and their diagnostic potential was evaluated. The sera of 25 patients infected with F. gigantica, 212 patients with other parasitic infections, 32 cholangiocarcinoma patients and 57 healthy controls were analysed. The sensitivity, specificity, accuracy, and positive and negative predictive values of this assay were the same with both peptides at 100%, 99·7%, 99·7%, 96·2% and 100%, respectively. These highly sensitive and specific peptide-based ELISAs for the detection of specific IgG4 antibody could be useful for laboratory diagnosis of human fascioliasis in future large-scale surveys throughout Southeast Asia where this disease is prevalent.

A statistical method that analyses correlation structures in families to delineate the contribution of genetic, household and environmental factors on clustering of infection, has been applied to data collected in an area endemic for brugian filariasis in South Sulawesi, Indonesia. Infection was assessed both by microfilaraemia and by anti-filarial IgG4. The results confirmed earlier findings that genetic factors play an important role in clustering of infection. When clustering of infection was analysed in children (<10 years of age) and adults (>20 years of age) separately, it was found that the genetic factors influence clustering of infection in children more profoundly than environmental or household effects. In contrast, genetic factors could not fully explain the clustering of infection seen in adults, which seemed to be mainly determined by household and environmental effects. The data have implications for genotyping studies in brugian filariasis; they indicate that it may be important to concentrate on the younger age groups where individual environmental effects have not yet overruled the genetic influences on gain/loss of infection.

In lymphatic filariasis, specific IgG4 responses to the parasite and their relationship with infection have been studied extensively, but only a few studies have concentrated on anti-filarial and total IgE. Here we have investigated the role of filarial infection pressure on production of IgE by considering length of exposure (age), filarial endemicity and parasitological status. Antibody levels were determined in 366 individuals, who were resident in 3 villages in South-Sulawesi, Indonesia, with varying degrees of filarial transmission intensity, as indicated by the prevalence of Brugia malayi microfilaraemia (0·7%, 9% and 32%, respectively). Anti-filarial IgE levels were significantly lower in the low transmission village than in the areas with intermediate and high filarial transmission; however, in the latter village a remarkable suppression of specific IgE was found. Microfilaria-positive individuals showed elevated levels of total IgE, but suppression of specific IgE, which has been reported before. Taken together, these observations suggest that 2 opposing mechanisms regulate anti-parasite IgE expression: increasing experience of filarial infection stimulates specific IgE, but antibody levels become specifically suppressed when microfilariae or adult worms develop. Using a simple mathematical model, we illustrate how anti-filarial IgE increases with parasite antigen up to a threshold level, but levels off and becomes down-regulated after the threshold is exceeded.

To dissociate the influence of host age from length of exposure on acquisition of filarial infection, we examined the development of microfilaraemia and anti-filarial IgG4 in all ages of a naive population that became suddenly exposed to Brugia malayi as a result of transmigration. Responses in 247 transmigrants, who had settled for periods of several months up to 6 years in their new homesteads, were compared with those of 133 life-long residents. As shown in earlier studies, anti-filarial IgG4 increased with age in the indigenous population, whose age is equivalent to length of exposure. However, by examining transmigrants, it became clear that development of specific IgG4 was influenced by age, since levels of this antibody were consistently higher in transmigrant adults than in transmigrant children, despite an equal length of exposure to filarial infection. Examining microfilaraemia, it was confirmed that infection establishes more rapidly in adults than in children.

We set out to study how anti-filarial IgG4 and IgE, which have been studied extensively in adult populations, are influenced by gender and by the degree of filarial endemicity during childhood. Development of specific IgG4 and IgE was examined in 502 children aged 3 months to 12 years, who were resident in 3 villages in South-Sulawesi with microfilaria prevalences of 6, 23 and 42%. Specific IgG4 and IgE could be detected as early as 18 months after birth, in low amounts, and increased to levels comparable to those produced by adults at the age of 3 years. A higher prevalence of anti-filarial IgG4 in boys, indicating higher filarial infection compared to girls, became apparent after the age of 7. The specific IgG4 response was strongly influenced by the degree of filarial endemicity and production of this antibody was considerably delayed in the low transmission village. With respect to IgE, it was noted that specific IgE was consistently higher in boys from infancy onwards indicating a predisposition for high IgE production in males. The influence of filarial endemicity was less profound on IgE than on IgG4. In conclusion, reactivity to filarial antigens begins early in life and is differentially influenced by gender and transmission intensity.

The present study was undertaken in village Karondang in South-Sulawesi, Indonesia, to investigate the influences of genetic, household and environmental factors on Brugia malayi infection. Infection status was determined by measuring both microfilariae in night blood and anti-filarial IgG4, as a marker for detection of active filarial infection. A total of 171 residents participated in the study; familial relationships between subjects were registered to construct pedigrees and distances between households were measured. The data were analysed using a test statistic for familial aggregation. For distribution of microfilariae over the study population a genetic influence on infection susceptibility was favoured over the household and environmental effects. For anti-filarial IgG4, all 3 clustering models gave significant results, suggesting that genetic, household and/or environmental factors influence specific IgG4 antibodies.