Journal of clinical immunology
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Autoinflammatory diseases are a group monogenic inflammatory conditions characterized by an early onset during childhood. ⋯ Under the term "periodic fevers" are gathered some monogenic diseases (familial Mediterranean fever, mevalonate kinase deficiency, and tumor necrosis factor receptor-associated syndrome) characterized by periodic or recurrent episodes of systemic inflammation causing fever often associated with rash, serositis (peritonitis, pleuritis), lymphadenopathy, arthritis, and other clinical manifestations. Systemic reactive (AA) amyloidosis may be a severe long-term complication. Cryopyrinopathies are a group of conditions associated to mutations of the gene Cryopyrin that are responsible for a spectrum of diseases (familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous and articular syndrome) characterized by a chronic or recurrent systemic inflammation variably associated with a number of clinical features, such as urticarial-like rash, arthritis, sensorineural deafness, and central nervous system and bone involvement. Other disorders are dominated by the presence of sterile pyogen abscesses prevalently affecting the skin, joints, and bones (pyogenic disorders). These include pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome, and Majeed syndrome. Finally, some diseases, such as Blau's syndrome, are characterized by the appearance of typical noncaseating granulomatous inflammation affecting the joints, skin, and uveal tract (granulomatous disorders). In the present review, we will focus on the clinical presentation of these disorders in childhood and report on the available therapeutic strategies.
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Pentraxins are a family of multimeric pattern-recognition proteins highly conserved in evolution. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein and serum amyloid P-component are classic short pentraxins produced in the liver, whereas the prototype of the long pentraxin family is PTX3. ⋯ In addition, PTX3 is essential in female fertility acting on the assembly of the cumulus oophorus extracellular matrix. Thus, PTX3 is a multifunctional soluble pattern recognition receptor acting as a nonredundant component of the humoral arm of innate immunity and involved in tuning inflammation, in matrix deposition and female fertility. Evidence suggests that PTX3 is a useful new serological marker, rapidly reflecting tissue inflammation and damage under diverse clinical conditions.
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Systemic sclerosis (SSc), also termed "scleroderma," is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Nramp 1 gene has multiple pleiotropic effects on macrophage activation pathways, including up-regulation of the chemokine/cytokine genes KC, tumor necrosis factor alpha, interleukin-1 b, inducible nitric oxide syntase, and major histocompatibility complex class II expression, as well as tumoricial activity and antimicrobial activity. ⋯ We found a significant association between INT4, (GT)n polymorphisms (p = 0.006 and 0.027, respectively), and SSc. Our findings suggest that NRAMP1 is a plausible candidate gene for SSc.
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Natural killer (NK) cell alloreactions against recipient cells in the setting of bone marrow transplantation have been associated with decreased rates of graft-versus-host disease (GVHD) and improved survival in transplant recipients with myeloid leukemia. These alloreactions are predicted by the absence of recipient HLA class I ligands for donor inhibitory killer Ig-like receptors (KIR). We hypothesized that donor NK cell alloreactions against recipient cells may affect the development of T and B-cell functions and incidence of GVHD in infants with severe combined immunodeficiency (SCID). ⋯ Analysis showed that the absence of a KIR ligand had no effect on the incidence or severity of GVHD (RR [corrected] = 0.95, p = 0.84), development of T-cell function (RR [corrected] = 1.05, p = 0.69), production of IgA (p = 0.46) or IgM (p = 0.33), or on 5-year survival (RR [corrected] = 1.21, p = 0.10). Further, in patients possessing native NK cells, the absence of KIR ligands in donors for recipient-inhibitory KIR did not alter transplantation outcomes. This study suggests that inhibitory KIR/HLA interactions do not play a significant role in bone marrow transplantation for SCID.
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While defective apoptosis predisposes to neoplasia, inappropriate apoptosis in the brain leads to permanent neurological deficits. Disregulated apoptosis has been implicated in several neurodegenerative disorders including Alzheimer's, Parkinson's, and Huntington's diseases. ⋯ FasL has also been implicated as a negative regulator for the inflammatory component of the demyelinating brain disorder multiple sclerosis (MS). Here, we discuss how FasL-mediated apoptosis may balance immune cell access to the brain with Alzheimer's disease and MS representing extremes of too little and too much immune access, respectively.