Isaac Melamed

Serum immunoglobulin A levels and ethnicity in an Israeli population sample

Serum IgA concentrations were measured in 1799 healthy Israeli military recruits (698 women and 1101 men) using an automated nephelometric system. The overall prevalence of IgA deficiency defined at a level of less than 50 mg/liter was 1.0 +/- 0.46% (95% confidence limits). No significant difference was found between the sexes in the mean values of serum IgA. Statistically significant ethnic differences were evident. Recruits of European origin had lower serum IgA concentrations than the North African, Israeli, or Asian origin groups. Whether the apparently high prevalence of IgA deficiency in this young population in Israel has clinical significance is at present unknown.

Subcutaneous Immunoglobulins: Product Characteristics and Their Role in Primary Immunodeficiency Disease

Research on the role of subcutaneous immunoglobulin in primary immunodeficiency disease (PIDD) is ongoing. We analyzed pivotal studies for four subcutaneous immunoglobulin products: IGSC 10% (Gammagard® Liquid), IGIV-C 10% (Gamunex®-C), IGSC 16% (Vivaglobin®) and IGSC 20% (Hizentra®). To identify similarities and differences between products, we examined infusion parameters, adverse event profiles and improvements in tolerability over time. Maximum volume infused was 30 mL/site for IGSC 10%, 34 mL/site for IGIV-C 10%, 15 mL/site for IGSC 16% and 25 mL/site for IGSC 20%. Maximum number of simultaneous infusion sites was 10 for IGSC 10%, 8 for IGIV-C 10%, 6 for IGSC 16% and 4 for IGSC 20%. Local adverse reaction rate per infusion was 0.02 for IGSC 10%, 0.59 for IGIV-C, 0.49 for IGSC 16% and 0.58 for IGSC 20%. IGSC products have similar efficacy profiles; however, their tolerability profiles vary. Reasons for these differences are unknown and warrant further research.

Coffee and the immune system

The effect of coffee consumption on the immune system, studied in 15 men and women, showed that the responses to PHA and Con A were about one-third lower during coffee drinking compared to a period of abstinence from coffee (117335, 99856 and 181236, 153315, P less than 0.004, 0.009 respectively). There was no effect on total T- or B-cells. There was no statistically significant change in the number of suppressor T-cells (20, 26; P = 0.1) or NK cells (20, 26; P = 0.014). Chemotaxis was higher in the coffee period at all concentrations. This exploratory study suggests that coffee intake modifies various measures of the immune function. The clinical relevance of the findings is not clear, and further studies aimed at delineating the constituents responsible for the effects observed are recommended.

Attention Deficit Disorder and Allergic Rhinitis: Are They Related?

The association between ADHD and allergy remains controversial. Our previous findings suggest that nerve growth factor may link the nervous and immune systems. The primary objective of this study was to determine if a combination of cetirizine + methylphenidate is effective in children with comorbid ADHD and allergic rhinitis. We also examined the role of nerve growth factor in these comorbidities. Our randomized, double-blind, placebo-controlled, crossover study enrolled 38 children diagnosed with comorbid ADHD and allergy using cetirizine (n = 12), sustained-release methylphenidate (n = 12), or cetirizine + methylphenidate (n = 14). Endpoints compared baseline to posttreatment evaluations for allergic rhinitis and ADHD scores. Serum nerve growth factor levels were measured using ELISA. For allergy endpoints, combination therapy produced results superior to individual therapy. For ADHD, similar scores were achieved for individual therapy; however, combination therapy resulted in improved scores. Nerve growth factor levels were downregulated following this trend. We conclude that ADHD and allergic rhinitis may have common mechanism and represent a comorbid condition that links the nervous system to the immune system. Further studies are needed.

A pilot study of high-dose intravenous immunoglobulin 5% for autism: Impact on autism spectrum and markers of neuroinflammation: Intravenous immunoglobulin 5% for autism

Research has shown that a subset of the autism spectrum disorder (ASD) population presents with immune dysregulation. To explore this topic further, we investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD. In this study, participants were recruited based on a diagnosis of autistic disorder, Aspergers disorder, or pervasive developmental disorder not otherwise specified. Participants also showed evidence of immune dysfunction based on abnormal levels of specific biomarkers, including CD40 ligand (CD154), lymphocyte stimulation, and T or B cell dysfunction. Of 17 screened patients, 14 completed the trial and received IVIG treatment (1 g/kg dose) for ten 21‐day treatment cycles. The primary endpoint was disease improvement assessed using standardized cognitive and behavioral tests (Childrens Communication Checklist [CCC‐2], Social Responsiveness Scale [SRS], Aberrant Behavior Checklist [ABC], Clinical Global Impressions‐Severity [CGI‐S] and ‐Improvement [CGI‐I], Autism Diagnostic Observation Schedule [ADOS], and Peabody Picture Vocabulary Test [PPVT]). Secondary endpoints included experimental biomarkers such as CD154, toll‐like receptor‐4, memory B cells, FOXP3, and lymphocyte stimulation. Significant improvements from baseline to study endpoint were observed in several subscales of the CCC‐2, SRS, CGI‐I, CGI‐S, and ADOS, including Associated Maladaptive Behaviors (Pu2009≤u2009.043), Reciprocal Social Interaction (Pu2009=u2009.015), Communication (Pu2009<u2009.001), and Stereotyped Behaviors and Repetitive Interests (Pu2009≤u2009.013). Statistically significant reductions were also seen in numerous secondary outcomes of immunological biomarkers indicative of neuroinflammation. IVIG was well tolerated; no subjects withdrew due to an adverse event, and clinical data showed no evidence of thromboembolic events. Autism Res 2018, 11: 421–433.

A new subset of common variable immune deficiency characterized by reduced C1 esterase inhibitor levels

factor receptor (BAFF-R) expression on CD19þ blood B cells from the patient (green) and a healthy control (dark purple). Mean fluorescence intensity (MFI) of BAFF-R staining is shown in the parentheses. This test was repeated twice with similar results. C, Sequence trace showing heterozygosity of a C>G mutation, leading to the missense mutation P21R. Trace is 1 of 2 that supported the mutation; alignments of both traces and the consensus is above the trace. Sequence alignment and the display was generated by Bionumerics software (www.applied-maths.com). Letters / Ann Allergy Asthma Immunol 115 (2015) 69e86 83