In our case series, we found a statistically significant difference in the CD3, CD4 and CD16/56 counts, compared to age-related reference values . In detail, most of the altered values were found in the oldest patients, aged 11–17 years (p < 0.05), suggesting that immunity plays an important role in protecting adolescents from ACNS infection. Few studies have highlighted T-lymphocyte alterations in patients with meningitis. In particular, a study conducted on 19 patients documented CD3, CD4 and CD16/56 lower level without any significant differences , congruous with other findings [16, 17].
Otherwise, most of the patients had normal complement levels. In literature as well, complements deficiencies are rarely linked to ACNS infections. Complement levels may increase or decrease in ACNS infections depending on the balance between complement production and consumption in each phase of the disease .
Immunoglobulin deficiencies are more associated to ACNS infections than primary complement deficiencies [19,20,21]. Usually, a combined IgG and IgA deficiency or IgG deficiency and neutrophil chemotaxis abnormality have been documented  In our study, all patients had normal IgA values while IgM and IgG levels were lower than the age-related standard. More specifically, IgG levels were significantly lower than the reference in most of our sample at the follow-up evaluation (p < 0.05).
Considering qualitative immunological tests, we observed that 51.4% of the eligible population had some B-lymphocyte proliferation abnormalities. Other reports have studied functional B cell alterations documenting low levels of B cell proliferations in patients with meningococceal meningitis .
To our knowledge, this is the first study correlating the causative pathogens to immune evaluation in ACNS infections. In particular, in our experience, Escherichia Coli, Klebsiella Pneumoniae and HI were more often isolated in patients younger than 3 years at diagnosis, who had at least one immunological alteration. Moreover, a broader variety of pathogens has been documented in patients with immunological abnormalities at all ages. Typical pathogens, such as NM and SP, were mostly observed in patients without any immune alteration.
Our study has some limitations. As in all retrospective studies, we could not consider the risk of developing the disease in subjects with a given immunodeficiency. Also, we did not have a control group, as we used the normal value reported in literature as a control. Moreover, despite evaluating patients at least 1 month after the admission, while in good clinical conditions, we could not exclude that the immune system dysregulation was a direct consequence of the ACNS infection rather than its cause. Finally, our study was based on a relatively small sample size, owing to the rarity of the disease.
Further studies are necessary to confirm our results as to evaluate the causal relationship between immunological status and clinical sequelae in patients with ACNS infections.