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Biomedical subjects

Wasu Kamchaisatian

Publications and source records attributed to Wasu Kamchaisatian.

9 recordsLinked to original sources

Validation of current joint American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma and Immunology guidelines for antibody response to the 23-valent pneumococcal vaccine using a population of HIV-infected children.

BACKGROUND: Measuring antibody responses to 23-valent pneumococcal polysaccharide vaccines (PPV) is crucial to evaluation of humoral immune function. However, data are limited comparing responses in immunodeficient subjects. OBJECTIVE: A case-controlled study comparing changes in PPV antibody titer in immunocompetent and immunodeficient children was performed to validate current guidelines. METHODS: A cohort of 95 immunocompetent children and 22 HIV-infected children, ages 2 to 15 years, was vaccinated with PPV, and before and after vaccination, IgG titers against capsular polysaccharides for 12 pneumococcal serotypes were measured. Results were used to calculate the receiver operator characteristic curve, sensitivity, and specificity of various interpretation criteria for their accuracy in detecting suboptimal responders. RESULTS: Immunodeficient subjects had lower CD4%, antidiphtheria, antitetanus titers, and mean post-PPV titers (2.5 +/- 1.7 vs 4.5 +/- 2.1 mug/mL; P < .001) compared with immunocompetent subjects. The interpretation, using individual post-PPV titer of > or =4-fold increase over prevaccination as a positive response, yielded the highest accuracy as measured by area under the curve value (receiver operator characteristic curve = .755). For this criterion, the numbers of serotypes with positive responses of < or =5 of 12 serotypes measured yielded 72.7% sensitivity and 56.8% specificity in detecting antibody-deficient subjects. CONCLUSION: Current guidelines using > or =4-fold increase in post-PPV titers has sufficient sensitivity and specificity to identify antibody deficiency. The minimal positive responses should be at least 50% of serotypes tested. CLINICAL IMPLICATIONS: Measurement of PPV antibody response based on the current guidelines accurately identify children with humoral immunodeficiency.

Acquired Immunodeficiency Syndrome↗

Four novel and three recurrent mutations of the BTK gene and pathogenic effects of putative splice mutations.

X-linked agammaglobulinemia is caused by mutations in the human BTK gene, leading to recurrent pyogenic infections. We describe four novel and three known BTK-mutations in seven patients from seven (six Thai and one Burmese) families. All but one were sporadic cases. Patients 1 and 2 had recurrent mutations in exon 10 (R288W) and exon 17 (R562W), respectively. Patient 3, a previously healthy individual who presented with pseudomonas sepsis with ecthyma gangrenosum had a known mutation in exon 17 (1749delT), leading to frameshift effect (F583fsX586). Patient 4 manifested with sepsis and concurrent acute appendicitis and pneumonia. He had a mutation, IVS8 + 1G > A, which led to an insertion of intron 8 into the transcripts. In Patient 5, a novel change in exon 7, c.588G > C, initially presumed Q196H, was found to cause a leaky splicing mutation, resulting in three distinct transcripts containing 17, 108, and 190 bp of the 5'-terminal of intron 7, which led to truncated peptides consisting of 203 and 211 amino acid residues (or Q196fsX204 and Q196fsX212, respectively). Patient 6 had a mutation in exon 14 (W421X), while patient 7 had a newly defined large deletion of exons 6-9. All of the mothers tested were mutation carriers. Transcript analysis in three mothers who were heterozygous for frameshift mutations revealed a minimal amount of aberrant transcripts, while their affected children had full expression of the mutant alleles, suggesting rapid degradation due to nonsense-mediated mRNA decay in the mothers. This is the first report of mutations of BTK from Thailand.

Agammaglobulinaemia Tyrosine Kinase↗

LMP-420, a small-molecule inhibitor of TNF-alpha, reduces replication of HIV-1 and Mycobacterium tuberculosis in human cells.

BACKGROUND: Co-infections of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (M. Tb) are steadily increasing and represent a major health crisis in many developing countries. Both pathogens individually stimulate tumor necrosis factor-alpha (TNF) release from infected cells and TNF, in turn, enhances the replication of each. A recent report on a Phase I clinical trial suggested that etanercept (soluble TNF receptor) might be beneficial in treating HIV/M. Tb co-infected patients. We sought to determine if a small molecule inhibitor of TNF synthesis and activity could block replication of either organism and thus be a potential adjunct to existing drugs targeting these agents. RESULTS: LMP-420, a novel anti-inflammatory agent that inhibits TNF, was tested for HIV-1 inhibition both alone and in combination with AZT (3' -azido-3-deoxythymidine). LMP-420 alone was tested against M. Tb. HIV-1 infected human peripheral blood mononuclear cells (PBMC) or M. Tb-infected human alveolar macrophages (AM) were treated with a single dose of LMP-420 and viral or bacterial replication determined after 7 or 5 days respectively. Viral replication was determined from supernatant p24 levels measured by ELISA. M. Tb replication was determined by bacterial culture of macrophage lysates. LMP-420 alone inhibited HIV replication over 7 days with an IC50 of approximately 300 nM. Combination of LMP-420 with AZT doubled the level of HIV inhibition observed with AZT alone. LMP-420 alone inhibited the replication of virulent M. Tb by >80%, more than that observed with anti-TNF antibody alone. CONCLUSION: Inhibition of TNF with inexpensive, small-molecule, orally-active drugs may represent a useful strategy for enhancing the activity of currently-available antiviral and anti-M. Tb agents, particularly in those areas where co-infections with these pathogens act to synergistically enhance each other.

Journal Article↗

Ocular manifestations in adolescent cystinosis: case report in Thailand.

Three siblings with a family history of consanguinity presented with short stature and two of the patients had leg deformity. None of them experienced ocular or renal symptoms at presentation. After the pediatricians found characteristics of Fanconi syndrome, an ophthalmic consultation was requested Ocular examination revealed typical cystine crystals deposited in the cornea and conjunctivae. No crystal deposits were found elsewhere in the eyes. Fundoscopic examination was normal. Two patients who underwent a complete ocular examination were diagnosed as adolescent cystinosis. The youngest patient who lost to follow up before completed ocular examination was suspected for adolescent cystinosis. This is the first report of cystinosis with ocular manifestation from Thailand.

Adolescent↗

Varicella zoster as a manifestation of immune restoration disease in HIV-infected children.

BACKGROUND: Exacerbation of opportunistic infections in HIV-infected patients shortly after initiation of highly active antiretroviral therapy (HAART) has been named immune restoration disease (IRD). Thus far, IRD has not been reported in children. OBJECTIVE: We describe the clinical and immune characteristics of IRD in HIV-infected children treated with HAART. METHODS: A historical cohort study was conducted in a tertiary HIV center in perinatally HIV-infected children who were started on a first stable HAART between January 1996 and July 2002. The incidence of opportunistic infections, newly AIDS-defining events or death after initiation of HAART, and virologic and immunologic information was evaluated at baseline and every 3 months post-HAART. RESULTS: Sixty-one perinatally HIV-infected children were started and maintained on HAART for >6 months. Seven episodes of IRD occurred. All were cutaneous herpes zoster (HZ). Children who developed HZ had significantly lower baseline CD4+ and CD8+ T-cell numbers compared with children who did not. HZ occurred only in children (7 of 34 subjects) with virological and immunological success to HAART. In children with a previous history of varicella infection, the risk of developing HZ after HAART was higher in those without a protective level of varicella-specific IgG (50%, or 5 of 10 subjects) compared with those with seroprotection (10%, or 2 of 20). CONCLUSION: Herpes zoster is a common manifestation of IRD in HIV-infected children after the initiation of HAART. Risks for developing HZ include no protective varicella-specific antibody despite previous varicella infection, severe immunodeficiency at baseline, and vigorous immunologic and virologic responses to HAART.

Antiretroviral Therapy, Highly Active↗

Effect of influenza virus vaccine on the expression of human immunodeficiency virus co-receptor CCR5.

BACKGROUND: Administration of influenza vaccine to human immunodeficiency virus (HIV)-infected children can lead to increased viral load. CCR5 and CXCR4 are known to play an important role in HIV cell entry and viral replication. OBJECTIVE: To determine the effects of influenza vaccine on chemokine receptors and on viral load in HIV-infected children. METHODS: Eight HIV-infected children receiving stable therapy and 11 healthy adults were enrolled. Chemokine expression and immune activation were determined before and 48 hours after influenza vaccination. CCR5 and beta-chemokine gene expression were analyzed using real-time polymerase chain reaction. Viral load was measured at baseline, 48 hours, and 6 to 12 weeks. RESULTS: Forty-eight hours after influenza vaccination, mean CCR5 expression was significantly decreased on the CD3 (21.1% vs 11.3% in HIV-infected children; P = .02; and 18.3% vs 10.7% in controls; P = .008) and CD4 (13.0% vs 3.6% in the HIV group; P = .04; and 13.6% vs 6.5% in controls; P = .02) lymphocytes. This was observed in conjunction with an increase in HLA-DR expression on T lymphocytes in HIV-infected children (P = .046). No significant changes were observed in HIV viral load, CD3 and CD8 lymphocyte counts, expression of interleukin 2 receptor and CXCR4, or gene expression of CCR5 and beta-chemokines 48 hours after vaccination. CONCLUSIONS: Influenza virus vaccine markedly decreased chemokine receptor CCR5 expression on CD4 T lymphocytes. However, this immunomodulatory effect does not seem to affect overall viral replication in HIV-infected children who received highly active antiretroviral therapy.

Antiretroviral Therapy, Highly Active↗

Immunogenicity of 23-valent pneumococcal polysaccharide vaccine in children with human immunodeficiency virus undergoing highly active antiretroviral therapy.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (23PSV) has been recommended for children infected with human immunodeficiency virus (HIV); however, the efficacy of this vaccination in HIV-infected children undergoing highly active antiretroviral therapy (HAART) has not been studied. OBJECTIVE: To study the immunogenicity and immunologic protection of 23PSV in HIV-infected children after stable HAART. METHODS: Serotype-specific IgG antibodies to 12 pneumococcal capsular polysaccharides were analyzed before and after 23PSV vaccination in 41 HIV-infected children undergoing HAART and compared with 95 HIV-negative control children. Seropositivity, clinical protection, and additional clinical protection from 23PSV were calculated based on serotype specific IgG antibody levels and on the known incidence of these serotypes for causing invasive disease. RESULTS: Children with HIV infection undergoing HAART developed a significant increase in specific IgG levels to Streptococcus pneumoniae after 23PSV vaccination (0.95 vs 1.84 micro/gmL, P < .001). The HIV-infected children with CD4+ cell counts of 25% or higher at the time of vaccination developed a higher additional clinical protection gain from 23PSV vaccination than did children with a lower percentage of CD4+ cells. CONCLUSIONS: HIV-infected children undergoing stable HAART develop a significant immunologic response to 23PSV, especially those with higher T-cell counts and lower viral loads at the time of vaccination.

Adolescent↗