Age-dependent deficiency in saliva and salivary antibodies secretion in Down's syndrome

Chaushu, Stella; Chaushu, Gavriel; Zigmond, Maora; Yefenof, Eitan; Stabholz, Adam; Shapira, Joseph; Merrick, Joav; Bachrach, Gilad

doi:10.1016/j.archoralbio.2007.06.002

Cited by 23 publications

(27 citation statements)

References 56 publications

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“…Along with severe mental and anatomical abnormalities, DS is associated with a wide range of immunodeficiencies (4). Included are deficiencies in adaptive immunity such as lymphopenia (5), impaired Ab response to immunization (6,7), as well as decreased levels of IgA (8). Deficits in innate immunity have also been identified primarily involving impaired neutrophil chemotaxis (9,10).…”

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confidence: 99%

Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Junkins

MacNeil

et al. 2013

The Journal of Immunology

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Respiratory tract infection with Pseudomonas aeruginosa is a common cause of hospitalization in immune-compromised individuals. However, the molecular mechanisms involved in the immune response to P. aeruginosa lung infection remain incompletely defined. In this study, we demonstrate that the regulator of calcineurin 1 (RCAN1) is a central negative regulator of inflammation in a mouse model of acute bacterial pneumonia using the opportunistic bacterial pathogen P. aeruginosa. RCAN1-deficient mice display greatly increased mortality following P. aeruginosa lung infection despite enhanced neutrophil recruitment and bacterial clearance. This mortality is associated with higher systemic levels of proinflammatory cytokines in RCAN1-deficient animals. These aberrant inflammatory responses coincide with increased transcriptional activity of proinflammatory RCAN1-target proteins NFAT and NF-κB. In addition, we reveal a novel regulatory role for RCAN1 in the ERK/STAT3 pathway both in vitro and in vivo, suggesting that aberrant STAT3 activity may significantly contribute to delayed resolution of inflammatory responses in our model. Together, these findings demonstrate that RCAN1 is a potent negative regulator of inflammation during respiratory tract infections.

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confidence: 99%

Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Junkins

MacNeil

et al. 2013

The Journal of Immunology

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“…While doses of myelosuppressive chemotherapy are typically adjusted during maintenance therapy, to maintain an adequate neutrophil count, this phase of treatment may nevertheless lead to B-cell depletion and hypogammaglobulinemia, and hence to a higher infection rate in already immunecompromised DS patients. 54,55 To reduce TRM, we suggest improving supportive care throughout the treatment period with aggressive treatment of infections and studies analyzing the potential benefit of antibacterial and antifungal prophylaxis and/or immunoglobulin substitution. Patients should be leukocyte depleted as non-DS patients during maintenance in order to prevent relapse, but with prompt interruptions for aplasia and with more intensive surveillance than non-DS children.…”

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confidence: 99%

Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group

Buitenkamp

Izraeli

Zimmermann³

et al. 2014

Blood

206

292

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Key Points• Although the risk of ALL relapse is significantly higher in children with DS, goodprognosis subgroups have been identified. • Patients with DS-ALL have higher treatment-related mortality throughout the treatment period independent of the therapeutic regimen.Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Münster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% 6 2% vs 15% 6 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% 6 1% vs 2.0% 6 <1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% 6 2% vs 81% 6 2%, P < .0001) and overall survival (74% 6 2% vs 89% 6 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] 5 0.58, P 5 .002), white blood cell (WBC) count <10 3 10 9 /L (HR 5 0.60, P 5 .005), and ETV6-RUNX1 (HR 5 0.14, P 5 .006) for EFS and age (HR 5 0.48, P < .001), ETV6-RUNX1 (HR 5 0.1, P 5 .016) and high hyperdiploidy (HeH) (HR 5 0.29, P 5 .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DSALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups. (Blood. 2014; 123(1):70-77)

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“…Down subjects in most of the studies were either children or young adults. Few of the selected studies included DS adults (Amano, et al, 2001;Chaushu, et al, 2007;Komatsu, et al, 2001;Sakellari, et al, 2005;. The median secretion rates of the specific antibodies in whole and parotid saliva were 70-77% and 34-60% (respectively) lower in young DS individuals as compared to young controls and farther 77-100% and 75-88% (respectively) lower in old DS compared to young DS.…”

Section: Resultsmentioning

confidence: 99%

“…Also, in DS patients with bone loss, it was noted that they have an increased level of sIgA, compared to those DS patients without bone loss. Chaushu et al (2007) assessed age-related changes in the salivary-specific humoral immunity of DS subjects. Parotid and whole saliva were collected from a young group of DS, an older group of DS individuals and compared to two age-matched groups of healthy volunteers.…”

Section: Antibody/immunoglobulin Productionmentioning

confidence: 99%

Down Syndrome and Periodontal Disease

Khocht¹

2011

Genetics and Etiology of Down Syndrome

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Age-dependent deficiency in saliva and salivary antibodies secretion in Down's syndrome

Cited by 23 publications

References 56 publications

Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group

Down Syndrome and Periodontal Disease

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