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Thyroid MALT lymphoma: self-harm to gain potential T-cell help.

ABSTRACT: The development of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is driven by chronic inflammatory responses and acquired genetic changes. To investigate its genetic bases, we performed targeted sequencing of 93 genes in 131 MALT lymphomas including 76 from the thyroid. We found frequent deleterious mutations of TET2 (86%), CD274 (53%), TNFRSF14 (53%), and TNFAIP3 (30%) in thyroid MALT lymphoma. CD274 was also frequently deleted, together with mutation seen in 68% of cases. There was a significant association between CD274 mutation/deletion and TNFRSF14 mutation (p = 0.001). CD274 (PD-L1) and TNFRSF14 are ligands for the co-inhibitory receptor PD1 and BTLA on T-helper cells, respectively, their inactivation may free T-cell activities, promoting their help to malignant B-cells. In support of this, both the proportion of activated T-cells (CD4+CD69+/CD4+) within the proximity of malignant B-cells, and the level of transformed blasts were significantly higher in cases with CD274/TNFRSF14 genetic abnormalities than those without these changes. Both CD274 and TNFRSF14 genetic changes were significantly associated with Hashimoto's thyroiditis (p = 0.01, p = 0.04, respectively), and CD274 mutation/deletion additionally associated with increased erythrocyte sedimentation rate (p = 0.0001). In conclusion, CD274/TNFRSF14 inactivation in thyroid MALT lymphoma B-cells may deregulate their interaction with T-cells, promoting co-stimulations and impairing peripheral tolerance.

SUBMITTER: Wu F

PROVIDER: S-EPMC8632687 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDeliberate Self-Harm (DSH) is a common problem among children and adolescents in clinical and community populations, and there is a considerable amount of literature investigating factors associated with DSH risk and the effects of DSH on the child. However, there is a dearth of research examining the impact of DSH on parents, and there are few support programmes targeted at this population. This cross-sectional study examines the profile of a sample of parents of young people with DSH who participated in a support programme (Supporting Parents and Carers of young people with self-harm: the SPACE programme), with the goal of investigating pre-test parental well-being, family communication, parental satisfaction, perceived parental social support, and child strengths and difficulties.MethodsParticipants were 130 parents who attended the SPACE programme between 2009 and 2012, and who completed six questionnaires at baseline: the General Health Questionnaire-12, Strengths and Difficulties Questionnaire, Kansas Parenting Satisfaction Scale, General Functioning Scale of the McMaster Family Assessment Device, Multidimensional Scale of Perceived Social Support, and a demographic questionnaire.ResultsThe majority of parents met criteria for minor psychological distress (86%) and rated the quantity and severity of their children's difficulties as being in the abnormally high range (74%) at baseline. A majority of participants (61%) rated their perceived social support as being poor. Lower parental well-being was significantly correlated with poorer family communication, poorer parenting satisfaction, and a greater number of difficulties for the child. Perceived social support was not significantly correlated with parental well-being. Parents whose children were not attending school at baseline had significantly lower well-being scores than those whose children were. Parents whose children had received a formal diagnosis of a mental health disorder also had significantly lower well-being scores than those whose children had not.ConclusionsParents of young people with DSH behaviours face considerable emotional and practical challenges; they have low levels of well-being, parenting satisfaction, social support, and experience poor family communication. Given the importance of parental support for young people with DSH behaviours, consideration should be given to the need for individual or group support for such parents.

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Thyroid MALT lymphoma: self-harm to gain potential T-cell help.

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