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Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23–dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.

ABSTRACTSome patients with common variable immunodeficiency (CVID) can generate an antibody response following vaccination with Neisseria meningitidispolysaccharide, but the duration of this protection is unknown. In this study, serum bactericidal antibody (SBA) responses to serogroup C N. meningitidisof 23 patients with CVID and 23 sex- and age-matched controls were measured 1 year after vaccination with the plain A/C meningococcal polysaccharide vaccine. The fold rise in serum bactericidal antibody geometric mean titers of the control group from prevaccination to 1 year postvaccination was significantly higher than that of the patient group (5.41- versus 2.96-fold, P= 0.009). Of 23 CVID patients, 8 had a poor response to vaccine (<4-fold rise) 3 weeks after vaccination, and low titers remained when measured 1 year later. Of the 15 CVID patients who had a normal response to vaccine (=4-fold rise) 3 weeks after vaccination, 6 cases failed to maintain protective SBA titers, whereas the remaining 9 had protective titers 1 year after vaccination. Only one of the 23 controls, who developed protective SBA titers after 3 weeks, lost the protective titers after 1 year. Among the patients, the presence of bronchiectasis and/or splenomegaly at enrollment was associated with poor SBA response to vaccine at 3 weeks and/or failure to maintain protective levels at 1 year. The results of this study demonstrate that a number of CVID patients can produce protective antibody titers that can persist for 1 year after vaccination, which lends strong support to the inclusion of polysaccharide vaccine in the immunization program for CVID patients.

ABSTRACTCommon variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and increased susceptibility to recurrent pyogenic infections. This study was performed to subclassify CVID on the basis of the bactericidal antibody responses of patients to polysaccharide meningococcal vaccine. Twenty-five patients with CVID (18 male and 7 female) and 25 healthy volunteers received meningococcal polysaccharide vaccine A + C. Serum bactericidal antibody (SBA) titers were measured at baseline and after 3 weeks. Response was correlated with clinical and immunological manifestations of CVID. Twenty-four (96%) of the 25 normal controls had a protective SBA titer of =8 postvaccination, whereas only 16 (64%) of the 25 CVID patients had a protective titer (Pvalue = 0.013). Among the patients with CVID who were nonresponders, there were significantly increased rates of bronchiectasis (P= 0.008), splenomegaly (P= 0.016), and autoimmunity (P= 0.034) in comparison with patients who had protective SBA titers. A reversed CD4/CD8 ratio was more common in the nonresponder group of patients (P= 0.053). We conclude that individuals with CVID who cannot produce protective postvaccination titers after receiving meningococcal polysaccharide vaccine are more likely to exhibit bronchiectasis, splenomegaly, and autoimmune diseases. Vaccination response may define subgroups of patients with CVID, enabling more effective monitoring and therapeutic strategies.

Primary immunodeficiency disorders (PID) are a heterogeneous group of diseases, characterized by an increased susceptibility to infections. A total of 930 patients (573 males and 357 females) are registered in Iranian PID Registry (IPIDR) during three decades. Predominantly antibody deficiencies were the most common (38.4%), followed by congenital defects of phagocyte number and/or function (28.3%), other well-defined immunodeficiency syndromes (17.7%), combined T- and B-cell immunodeficiencies (11.0%), complement deficiencies (2.4%), and diseases of immune dysregulation (2.3%). Common variable immunodeficiency was the most frequent disorder (20.8%), followed by chronic granulomatous disease, ataxia-telangiectasia, btk deficiency, selective IgA deficiency, and T-B-severe combined immunodeficiency. The frequency of other PID disorders was less than 50 in number (<5%). There is an increasing trend in recognition of more PID in the recent years. Construction of such registry is not only important for its epidemiological aspect but also for its role in increasing the physician's knowledge about such disorders.

Alloimmunization to donor blood group antigens remains a significant problem in transfusion medicine. A proposed method to overcome donor−recipient blood group incompatibility is to mask the blood group antigens by the covalent attachment of poly(ethylene glycol) (PEG) to the red blood cell (RBC) membrane. Despite much work in the development of PEG-coating of RBCs, there is a paucity of data on the optimization of the PEG-coating technique; it is the aim of this study to determine the optimum conditions for PEG coating using a cyanuric chloride reactive derivative of methoxy-PEG as a model polymer. Activated PEG of molecular mass 5 kDa was covalently attached to human RBCs under various reaction conditions. Inhibition of binding of a blood-type specific antiserum (anti-D) was employed to evaluate the effect of the PEG-coating, quantified by hemocytometry and flow-cytometry. RBC morphology was examined by light and scanning electron microscopy. Statistical analysis of experimental design together with microscopy results showed that the optimum PEGylation conditions are pH 8.7, temperature 14 °C, and reaction time 30 min. An optimum concentration of reactive PEG could not be determined. At high polymer concentrations (>25 mg/mL) a predominance of type III echinocytes was observed, and as a result, a concentration of 15 mg/mL is the highest recommended concentration for a linear PEG of molecular mass 5 kDa.

ABSTRACTCommon variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and recurrent bacterial infections. The records of 65 patients with CVID (37 males and 28 females) in the age range of 24 to 537 months were reviewed. By the year 2003, 11 patients had died and seven patients could not be located. The total follow-up period was 221 patient-years. The median diagnostic delay (time between onset and diagnosis) in our patient group was 60 months. At the time of diagnosis, the baseline serum immunoglobulin G (IgG), IgM, and IgA levels were below the level normal for the patients' age; the medians for this group were 120, 10, and 0 mg/dl, respectively. All of the patients presented with infectious diseases at the time of onset, the most common of which were otitis media, diarrhea, pneumonia, and sinusitis. Acute and recurrent infections were also found in almost all of the patients, particularly involving respiratory and gastrointestinal systems. The most common infections, before diagnosis and during follow-up, were pneumonia, acute diarrhea, acute sinusitis, and otitis media. CVID should be considered in any patient with a history of recurrent infections and decreased levels of all serum immunoglobulin isotypes.

Inherited neutropenia is characterized by a decrease in the absolute number of circulating neutrophils and an increased susceptibility to infections. The current study was performed to determine the clinical and laboratory findings of Iranian patients with inherited neutropenias. Records of 26 patients (14 male, 12 female) with inherited neutropenia were reviewed in this study. The patients had been referred to Children's Medical Center, a referral center for immunodeficiency disorders in Iran, during a 22-year period (1981-2003). Primary immunodeficiency disorders of these patients were as follows: cyclic neutropenia (8 patients), Shwachman-Diamond syndrome (7 patients), Kostmann syndrome (6 patients), and Chediak-Higashi syndrome (5 patients). The mean absolute neutrophil count of patients was 398.2 ± 259.3 cells/mm3(range 74-1,152/mm3) at the first visit. Twenty-one patients showed severe, four moderate, and one mild neutropenia. Sixteen of these patients had leukopenia, seven anemia, two thrombocytopenia, and one monocytosis. The most common presenting complaints in these patients were oral ulcer, otitis, pneumonia, diarrhea, cutaneous abscess, and oral candidiasis. The patients first manifested symptoms of infection suggesting neutropenia at a median age of 7.5 months (range 1 month to 10 years). During follow-up, respiratory infections developed in 24 cases, oral manifestations in 20 patients. The most common infections, in descending order of frequency, were otitis media, abscesses, pneumonia, oral ulcers, acute diarrhea, cutaneous infections, oral candidiasis, and periodontitis. Less frequent infections were sinusitis, cystitis, conjunctivitis, meningitis, and osteomyelitis. Nonspecific symptoms (hepatomegaly and splenomegaly) were also detected in 10 patients and 1 patient, respectively. Three patients died of recurrent infections. The infectious manifestations both at presentation and during follow-up in inherited neutropenia were similar. Although inherited neutropenias are rare, recurrent infections always deserves further evaluation for detecting such disorders.

Summary Using the method of bibliometrics, a 1999-2002 biochemistry and molecular biology database was constructed for China from the Science Citation Index Expanded (SCI-Expanded). Based on this database, the author quantitatively analyzed the current research activity in biochemistry and molecular biology in China. Results show that almost half the publications were published in Chinese journals. The percentage of articles published by Chinese authors in the total articles from the world is increasing. The number of articles published in high influence journals is continuously increasing. The research outputs are mainly located in Beijing, Shanghai and Hong Kong. The sites of the China Science Academy and National Universities are the important locations for these studies. The collaboration rate of Chinese output is low as compared to results from other countries. USA and Japan are the main international collaborating countries.

The prevalence of allergic disease has increased world wide during the last decades. Pollen allergy is the most typical form of allergic disease. The increase in its frequency during recent years is the most evident. Environmental factors play an important role in the problem of pollen allergy in large cities. The aim of this research is determination of allergenicity of Canna pollen in polluted and non-polluted conditions, detection of their allergenic proteins and also elucidation of some microscopic effects of air pollutants on pollen structure and proteins. Mature and immature pollen grains of Canna indicawere collected from polluted and non-polluted areas. Pollen grains were studied by scanning electron microscopy. Mice were sensitized by injection of pollen extract and an adjuvant for five times. Allergy potency of different pollen extracts were compared by means of skin test, blood eosinophills number and IgE levels in sensitized and treated animals. Pollen proteins were studied by SDS-PGE and allergenic proteins were detected by immunoblotting techniques. Scanning electron microscope study of the pollen grains showed that in polluted areas, air born particles accumulated on the surface of pollen and changed both pollen's shape and pollen's tectum. Also many vesicles were released out of polluted pollen and the pollen material agglomerated on the surface of pollen. SDS-PAGE showed that different proteins exist in mature and immature pollen. In pollen collected from polluted area, some of protein bands between 22 and 45 kDa were disappeared . Also in all polluted pollen grains, protein content of pollen decreased in response to air pollution causing the release of pollen proteins. According to our experiments and regarding induction of allergic symptoms, the polluted pollen is more effective than non-polluted one, and mature pollen has more allergy potency than immature one.

Although long-term intravenous immunoglobulin infusion is an effective treatment for children with antibody deficiencies, it can be complicated by systemic adverse reactions.