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Advanced Neurology Role of immunosuppressants in autism

against viral infections. In research on the innate immune authors claimed that there is an increase in the level of
system and immunological regulation, NK cells and their a gene associated with NK cells in the peripheral blood
interactions with the nervous system were shown to play cells of early infants who suffer from ASD. Natural killer
a significant role. Immunological dysregulation leads to cells release a wide variety of cytokines that promote
inappropriate immune responses to internal and external inflammation. Interferon-gamma and TNF-α are two
stimulations, which can lead to neurodevelopmental examples of these cytokines. In NK cells, an unusual CD56
disorders, particularly in the developing brain . Children dim HLA-DR+ NKG2Chigh KIR2DL1+ phenotypic profile
[29]
with ASD had more NK cells, higher levels of cytotoxicity was discovered to be persistent. This signature was found
when not stimulated, and lower levels of cytotoxicity when to be related to the core clinical characteristics of ASD. The
stimulated. In addition, genetic factors that affect NK cell authors of the study found this to be the case. The presence
modification include overexpression of SPON2, IL2RB, of NK cells in the CNS may be suggestive of much more
CX3CR1, and GZMB as well as reduced expression of direct central effects of their abnormality; the evaluation of
[84]
HMGB3, NMUR1, and altered STAT4 DAS . Greater NK which will require additional research .
[29]
cell counts, up to 40% higher, have been reported in people We discovered that there is a link between Lyme disease
with ASD. KIR and HLA are two of the NK cell receptors. and autism by studying these NK cells. Lyme disease and
Human leukocyte antigen gene (HLA) produces autism share many neurological traits. Involvement of
proteins found in all nucleated cells, and these proteins both white and matter, antibodies against myelin basic
are connected to killer immunoglobulin-like receptors protein, hypoperfusion (restricted blood supply to the
(KIR). KIR is encoded through the leukocyte receptor brain), thyroid antibodies, and gastrointestinal paralysis
complex by NK cells while they are under the influence are some of the examples. Children with autism have
of HLA ligands. This occurs when NK cells attach to been discovered to have low CD57 NK cells, which may
cell surface receptor proteins . KIR2DS2 levels are be a result of the neurological Borrelia complex. This is in
[81]
found to be significantly higher in children diagnosed contrast to the musculoskeletal presentations of Lyme that
[85]
with ASD in comparison to those found in the general are also common in these children, as shown in Figure 3 .
population and those found in inhibitory KIR. An In view of this, we believe that further investigation in
increased immunological activation in pregnant mothers the field of NK cells would strengthen research on the
throughout pregnancy indicates an increased risk of ASD treatment of autism.
in children . According to the study’s findings, mothers 3.2.1. Synaptic pruning relationship with NK cells
[82]
of autistic children have a statistically significant decrease
in the KIR(AA) haplotype when compared to mothers Natural killer cells are lymphocytes that play a critical role
of normal children. Furthermore, the HLA C1 allotype in the immune system’s defense against viruses and cancer.
interacts with KIR 2DS1, stimulating NK cells; KIR2DS1 is Recent studies have also suggested that NK cells may play
[29]
found in women whose children having ASD , and KIR a role in brain development and function, particularly in
are important components of both the innate and adaptive the regulation of synaptic plasticity and the elimination of
immune systems because they are found in NK cells. weak or unnecessary synapses. There is some evidence to
About 14 KIR genes, including inhibitory and activating suggest that NK cells may be involved in the pathogenesis
forms, are located on chromosome 19q13.4. HLA ligands of ASD, although the exact mechanisms are not yet clear.
regulate NK cells through binding to cell surface receptor For example, studies have shown alterations in NK cell
proteins encoded in the leukocyte receptor complex activity and cytokine levels in children with ASD, as well
(LRC) on chromosome 19q13.4. There are six key receptor as changes in the expression of genes involved in NK
[86,87]
complexes, one of which is the KIR, that contribute to the cell function . Taken together, these findings suggest
regulation of NK cell behavior. As in the pathology of other that there may be a complex interplay between caspase-
mediated synaptic pruning, NK cell function, and ASD
diseases, interactions between HLA and KIR may play a pathogenesis. The role of NK cells in brain development
significant role in autism. On stimulation with K562 target and function is a relatively new area of research. It is
cells, Warren et al. found reduced NK death in cells from thought that NK cells may be involved in the regulation
ASD participants .
[28]
of microglial function, which, in turn, plays a critical role
Reductions in NK cell killing in response to K562 cells in synaptic pruning and brain development. NK cells may
were also observed in a study by Enstrom et al. 11 also be involved in the elimination of synapses directly,
[83]
KIR receptor probes were found to be overexpressed although the mechanisms underlying this process are
in ASD individuals, nine of which were inhibitory KIR not clear yet. Alterations in synaptic pruning have been
genes, according to the microarray investigation . The implicated in the pathogenesis of several neurological and
[84]

Volume 2 Issue 2 (2023) 9 https://doi.org/10.36922/an.391