An Atypical Autoinflammatory Disease Due to an LRR Domain NLRP3 Mutation Enhancing Binding to NEK7

Journal of Clinical Immunology - The NLRP3 inflammasome is a vital mediator of innate immune responses. There are numerous NLRP3 mutations that cause NLRP3-associated autoinflammatory diseases...     

Polysaccharide antibody responses are impaired post bone marrow transplantation for severe combined immunodeficiency,but not other primary immunodeficiencies

Established treatment of severe combined immunodeficiencies (SCID) and other primary immunodeficiencies (PID) is bone marrow transplantation (BMT). Normal lymphocyte numbers and protein antigen responses are present within 2 years of BMT, polysaccharide antibody responses appear last. Streptococcus pneumoniae infection causes significant morbidity and mortality post-BMT. Previous studies have shown good protein antigen responses post-BMT for SCID and PID, but had not examined the polysaccharide responses. We retrospectively analysed pneumococcal polysaccharide (PPS) responses in our patient series.In total, 22 SCID and 12 non-SCID PID were evaluated, all >2 years post BMT: 17 SCID, 12 PID received chemotherapy conditioning; 17 SCID, three PID had T-cell depleted (TCD) BMT, others had nonconditioned whole marrow BMT. All had normal Haemophilus influenza B and tetanus antibody responses. Of 22 SCID, 13 vs 11/12 PID responded to PPS vaccine (P=0.05). There was no association with donor age, GvHD, B-cell chimerism, or IgG2 level. Fewer TCD marrow recipients responded to PPS (P=0.04). Analysis of the SCID group showed no association of PPS response with type of marrow received. This is the first study to specifically examine PPS antibody responses following SCID and PID BMT. Pneumococcal conjugate vaccine antibody responses should be examined in these children.     

The influence of dietary phosphate on the toxicity of orally ingested lead in rats

The influence of elevated dietary phosphate on the toxicity of orally ingested lead was investigated in male weanling Wistar rats. Two groups of 20 rats were fed diets containing either adequate (0.5%) or high (1.2%) levels of phosphorus (as phosphates). Half of the rats on each level of phosphorus were given 20 μg lead (as lead acetate)/g dry diet. After 8 wk, biochemical tests for lead toxicity were carried out and tissue-lead levels were measured. All of the given lead-supplemented diets had higher concentrations of lead in bone, brain, kidney and liver than those given diets without added lead but the increase was significantly greater in all tissues in the group given the 1.2% phosphorus diet. Lead supplementation increased the levels of free erythrocyte protoporphyrin and decreased the activity of δ-aminolaevulinic acid dehydratase. The lead-induced increase in the level of free erythrocyte protoporphyrin was no greater in the high-phosphate group than in the low-phosphate group but the decrease in δ-aminolaevulinic acid dehydratase activity was significantly larger in the high-phosphate group. This work demonstrates that excess dietary phosphate significantly increases lead toxicity and indicates the need for continued research on the interaction between dietary factors and lead toxicity.     

Oxidation of erythrocyte glutathione by monocytes stimulated with interleukin-6: Analysis by H spin echo NMR

¹H spin echo NMR was used to follow the release of reactive oxygen species (ROS) from human monocytes by monitoring erythrocyte glutathione status, which is sensitive to applied oxidative stress. This allowed the ability of the cytokine interleukin-6 (IL-6) to stimulate release of ROS from monocytes to be assessed in terms of oxidative damage to other cells, providing an estimation of its importance in vivo. It was found that incubation of monocytes with erythrocytes in the presence of IL-6 resulted in oxidation of the erythrocyte glutathione pool, indicating that oxidants are released in sufficient amounts to cause oxidative stress. High levels of IL-6 occurring in plasma of women with severe pre-eclampsia could therefore be responsible for depleted plasma antioxidants and haemolysis. The oxidation of erythrocyte glutathione was inhibited by the presence of the cyclooxygenase inhibitor indomethacin, suggesting that this may be of value in the treatment of oxidative pathologies.     

Lymphocyte subsets in term and significantly preterm UK infants in the first year of life analysed by single platform flow cytometry

This observational study describes the ranges observed for lymphocyte subsets for significantly preterm infants (<32 weeks) in the first year of life, measured by single platform flow cytometry and compared to identically determined subsets in term infants. After ethical approval 39 term and 28 preterm infants had lymphocyte subset analysis before and after their primary immunization series. Median values with 5th and 95th percentiles of absolute counts and percentages are presented for total lymphocytes, T cells, NK cells, B cells, cytotoxic T cells, helper T cells, dual positive T cells, activated T cells, activated T helper cells (including T regulatory cells), pan memory T cells, pan naive T cells, memory helper T cells, naive helper T cells and the T helper/suppressor ratio. The lymphocyte profile of the preterm infants differed from that of the term infants.     

Pitfalls of formalin fixation for determination of antineutrophil cytoplasmic antibodies

Sera can produce nuclear or perinuclear immunofluorescence staining in neutrophils which may be caused by antibodies with differing antigenic specificities. These include perinuclear antineutrophil cytoplasmic antibodies (P-ANCA), granulocyte specific antinuclear antibody (GS-ANA), and antinuclear antibody (ANA). There is controversy over the value of formalin fixation of neutrophils in differentiating antibodies giving selective or preferential reaction with the nuclear or perinuclear area of neutrophils. In a comparative study of 77 sera, formalin fixation caused inconsistency, nonspecific effects, and false positivity owing to enhanced fluorescence. If formalin fixed neutrophils are used in the routine diagnostic laboratory, this will add confusion to the interpretation of the ANCA assay.