Soluble HLA measurement in saliva and cerebrospinal fluid in Caucasian patients with multiple sclerosis: a preliminary study

Adamashvili, Irena; Minagar, Alireza; Gonzalez‐Toledo, Eduardo; Featherston, Liubov; Kelley, Roger E.

doi:10.1186/1742-2094-2-13

Cited by 18 publications

(6 citation statements)

References 37 publications

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“…Because of this lack of specificity for the peptide presented, any conformationally correct sMHCI is a potential ligand, which may be why neurons are sensitive to such low levels of sMHCI. Notably, little or no sMHCI is detected in CSF of healthy individuals [30] indicating that the blood brain barrier effectively blocks sMHCI in peripheral blood from entering the CNS. Consequently, the level of MHCI expression in a particular brain region may be the major regulator of local sMHCI levels.…”

Section: Discussionmentioning

confidence: 99%

A Potential Role for Shed Soluble Major Histocompatibility Class I Molecules as Modulators of Neurite Outgrowth

et al. 2011

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The neurobiological activities of classical major histocompatibility class I (MHCI) molecules are just beginning to be explored. To further examine MHCI's actions during the formation of neuronal connections, we cultured embryonic mouse retina explants a short distance from wildtype thalamic explants, or thalami from transgenic mice (termed “NSE-Db”) whose neurons express higher levels of MHCI. While retina neurites extended to form connections with wildtype thalami, we were surprised to find that retina neurite outgrowth was very stunted in regions proximal to NSE-Db thalamic explants, suggesting that a diffusible factor from these thalami inhibited retina neurite outgrowth. It has been long known that MHCI-expressing cells release soluble forms of MHCI (sMHCI) due to the shedding of intact MHCI molecules, as well as the alternative exon splicing of its heavy chain or the action proteases which cleave off it's transmembrane anchor. We show that the diffusible inhibitory factor from the NSE-Db thalami is sMHCI. We also show that COS cells programmed to express murine MHCI release sMHCI that inhibits neurite outgrowth from nearby neurons in vitro. The neuroinhibitory effect of sMHCI could be blocked by lowering cAMP levels, suggesting that the neuronal MHCI receptor's signaling mechanism involves a cyclic nucleotide-dependent pathway. Our results suggest that MHCI may not only have neurobiological activity in its membrane-bound form, it may also influence local neurons as a soluble molecule. We discuss the involvement of complement proteins in generating sMHCI and new theoretical models of MHCI's biological activities in the nervous system.

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Section: Discussionmentioning

confidence: 99%

A Potential Role for Shed Soluble Major Histocompatibility Class I Molecules as Modulators of Neurite Outgrowth

et al. 2011

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“…In the search for novel diagnostic salivary biomarkers for MS, Adamashvili et al. [216] determined, using ELISA, that the concentration of HLA class II is significantly elevated in the saliva of patients with Relapsing Remitting MS (RRMS) compared to healthy controls. HLA class I were not detected by the used technique, even though they are found in low concentrations in saliva.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Salivary biomarkers for the diagnosis and monitoring of neurological diseases

et al. 2018

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Current research efforts on neurological diseases are focused on identifying novel disease biomarkers to aid in diagnosis, provide accurate prognostic information and monitor disease progression. With advances in detection and quantification methods in genomics, proteomics and metabolomics, saliva has emerged as a good source of samples for detection of disease biomarkers. Obtaining a sample of saliva offers multiple advantages over the currently tested biological fluids as it is a non-invasive, painless and simple procedure that does not require expert training or harbour undesirable side effects for the patients. Here, we review the existing literature on salivary biomarkers and examine their validity in diagnosing and monitoring neurodegenerative and neuropsychiatric disorders such as autism and Alzheimer's, Parkinson's and Huntington's disease. Based on the available research, amyloid beta peptide, tau protein, lactoferrin, alpha-synuclein, DJ-1 protein, chromogranin A, huntingtin protein, DNA methylation disruptions, and micro-RNA profiles display a reliable degree of consistency and validity as disease biomarkers.

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“…Generally, HLAs are expressed in the surface of the cells responsible for the immune response. HLAs are also present in a soluble form (sHLA) in biological fluids, from which they can be quantified [87][88][89]. In MS, HLA-II regulates the immune response through the activation of cells directed against the myelin sheath.…”

Section: Salivary Biomarkers In Multiple Sclerosismentioning

confidence: 99%

“…In conclusion, the results of the study demonstrated that the levels of sHLA-II showed a similar trend to that observed in the CSF. Furthermore, the possible correlation of sHLA to disease suggests that salivary sHLA could be used as a potential biomarker for the diagnosis of MS [89].…”

Section: Salivary Biomarkers In Multiple Sclerosismentioning

confidence: 99%

Salivary Biomarkers: Future Approaches for Early Diagnosis of Neurodegenerative Diseases

et al. 2020

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Many neurological diseases are characterized by progressive neuronal degeneration. Early diagnosis and new markers are necessary for prompt therapeutic intervention. Several studies have aimed to identify biomarkers in different biological liquids. Furthermore, it is being considered whether saliva could be a potential biological sample for the investigation of neurodegenerative diseases. This work aims to provide an overview of the literature concerning biomarkers identified in saliva for the diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Specifically, the studies have revealed that is possible to quantify beta-amyloid1–42 and TAU protein from the saliva of AD patients. Instead, alpha-synuclein and protein deglycase (DJ-1) have been identified as new potential salivary biomarkers for the diagnosis of PD. Nevertheless, future studies will be needed to validate these salivary biomarkers in the diagnosis of neurological diseases.

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Soluble HLA measurement in saliva and cerebrospinal fluid in Caucasian patients with multiple sclerosis: a preliminary study

Abstract: Background: Measurement of soluble HLA in body fluids has a potential role in assessing disease activity in autoimmune disorders.

Cited by 18 publications

References 37 publications

A Potential Role for Shed Soluble Major Histocompatibility Class I Molecules as Modulators of Neurite Outgrowth

A Potential Role for Shed Soluble Major Histocompatibility Class I Molecules as Modulators of Neurite Outgrowth

Salivary biomarkers for the diagnosis and monitoring of neurological diseases

Salivary Biomarkers: Future Approaches for Early Diagnosis of Neurodegenerative Diseases

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