Safety of vaccinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation.

Reactivation of varicella zoster virus (VZV), clinically manifested as herpes zoster (HZ) is a common complication after hematopoietic stem cell transplantation (HSCT). The optimum prophylaxis for this disease has not been defined. In this study, we examined the effects of vaccinating donors with a live-attenuated vaccine with particular reference to their immune responses and the outcome of HSCT patients. Forty prospective HLA-matched sibling donors were vaccinated before HSCT. There were humoral immune responses in both sero-positive (P<0.01) and sero-negative (P=0.058) donors. Cellular immune response was assayed in 26 donors. Significant correlation was observed between cellular immune responses as enumerated by thymidine incorporation and interferon gamma secretion (P<0.001) and the latter was used in subsequent analyses. Significant response was observed in sero-negative (6/26) and a group of sero-positive (13/26) donors while 7/26 sero-positive donors showed no response. Thirty-four HSCT were performed. These patients have a lower, albeit insignificant, risk of HZ compared with historical controls and only 3/34 patients developed single dermatomal HZ at 6, 9 and 28 months after HSCT. No patients developed VZV-related mortality. Vaccinating donors with live-attenuated VZV vaccine was safe, but whether it confers a significant protection to the patients would require further study.

Anti-cyclic citrullinated peptide: diagnostic and prognostic values in juvenile idiopathic arthritis and rheumatoid arthritis in a Chinese population.

OBJECTIVE: The incidence and clinical significance of anti-cyclic citrullinated peptide (CCP) antibodies in a cohort of Chinese patients with juvenile idiopathic arthritis (JIA) and adults with rheumatoid arthritis (RA) were studied. METHODS: Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 59 patients with JIA, 129 adult RA patients, 48 children with diseases other than JIA, 68 adult patients with rheumatic diseases other than RA, and 60 normal adults. Associations between anti-CCP antibodies and clinical and laboratory parameters were determined by Fisher's exact test. RESULTS: Six of 59 (10.2%) patients with JIA and 71 of 129 (55%) patients with RA were positive for anti-CCP. Four of five RF-positive JIA patients and two of 54 RF-negative JIA patients were positive (p<0.001). One paediatric patient with allergy (0.9%) and two adult patients with rheumatic diseases other than RA (2.3%) were positive. All healthy controls were negative for anti-CCP. The specificity was 99.1% for JIA and 98.4% for RA. The sensitivity was 10.2% for JIA and 55% for RA. Positive predictive values were 85.7% for JIA and 97.3% for RA and negative predictive values were 66.9% for JIA and 68.5% for RA. CONCLUSION: The anti-CCP antibody assay is a valuable tool for the diagnosis of RA and a subset of JIA in Chinese patients. It could be a useful predictive test for joint erosion in JIA of the polyarticular RF-positive subset and may be influential in the choice of the best therapeutic strategy in patients with recent-onset arthritis.

Chronic benign neutropenia among Chinese children.

OBJECTIVE: To delineate the clinical behaviour of chronic benign neutropenia in Chinese children in Hong Kong. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS: All infants and children with absolute neutrophil count of 1.5 x 10(9) /L or lower for more than 3 months. MAIN OUTCOME MEASURES: Development of significant infection, and achievement of remission. RESULTS: Twenty-four children with chronic benign neutropenia were identified between 1992 and 2001. Their median age of diagnosis was 9 months. The mean (standard deviation) initial absolute neutrophil count was 0.28 x 10(9) /L (0.24 x 10(9) /L). Twenty-three patients presented with infection. Of the 19 patients tested, four (21%) were positive for anti-neutrophil antibodies. Bone marrow examination was performed in 17 patients: nine had normal results, but six showed evidence of peripheral consumption, one showed late maturation arrest at band stage, and one showed phagocytosis of myeloid cells by histiocytes. The overall hospitalised infection rate was 51.6 episodes per 1000 patient-months. Ten percent of cases were considered 'significant' infections and required hospital admission with either surgical intervention or intravenous therapy (antibiotics or fluid replacement). In the first year of diagnosis, more than 80% of patients had their lowest absolute neutrophil count (mean, 0.16 x 10(9) /L; standard deviation, 0.11 x 10(9) /L). Granulocyte-colony stimulating factor was used to treat three patients and induced transient elevation of absolute neutrophil count in all three. The projected remission rate was 55.4% at 3 years. Even for those with persistent disease, there was significant recovery in absolute neutrophil count to a mean of 0.5 x 10(9) /L (P<0.01). CONCLUSIONS: Patients with chronic benign neutropenia experienced a relatively benign clinical course regardless of their remission status. Only a small proportion of patients developed significant infections. A multi-centre prospective study may help identify predictive factors of remission.

Antirecipient helper and cytotoxic T-cell frequencies in bone marrow transplantation.

We assayed helper T-lymphocyte precursor frequencies (HTLPf), interferon (IFN)-gamma-producing cell frequencies (IFN-gammaPf) and CTL precursor frequencies (CTLPf) to see if they could predict the severity of acute graft-versus-host disease (aGVHD) and disease relapse after transplantation. In all, 48 bone marrow transplantation (BMT) patients and their HLA-identical sibling (n=29) or matched unrelated donors (MUD) (n=19) were recruited. HTLPf, IFN-gammaPf and CTLPf were measured using a limiting dilution assay (LDA). Patients were followed prospectively to assess the severity of aGVHD and the status of the primary disease after BMT. High (>5 x 10(-6)) HTLPf, CTLPf and IFN-gammaPf were significantly associated with the occurrence and severity of aGVHD in patients who received transplants from HLA-identical sibling. Among patients receiving BMT from MUD, HTLPf and CTLPf, but not IFN-gammaPf, were associated with aGVHD. Five patients had disease relapse post-BMT and the risk was not significantly associated with HTLPf, CTLPf or IFN-gammaPf. Patients with high (>5 x 10(-6)) HTLPf, IFN-gammaPf or CTLPf before BMT are at higher risk of developing aGVHD after transplantation from both matched sibling donors and MUD. Whether these parameters can predict disease relapse would have to be investigated with a larger cohort of patients.

Immunologic profile of patients with protein-losing enteropathy complicating congenital heart disease.

The immunologic profile of patients with congenital heart disease complicated by protein-losing enteropathy (PLE) is undefined. The aim of this study was to assess the lymphocyte subpopulation and immunglobulin (Ig) pattern in patients with PLE complicating congenital heart disease. The immunologic profile of six patients with congenital heart disease complicated by PLE was compared to that of controls without PLE matched for age and cardiac interventions. Enteric protein loss was documented by Tc99m-labeled albumin scintigraphy. The lymphocyte subpopulations were enumerated using flow cytometry, whereas serum IgG, IgA, and IgM concentrations were measured by the turbidimetric technique. The cardiac diagnoses included complex cyanotic heart disease post-Fontan procedure (n = 3), and one each of tetralogy of Fallot, restrictive cardiomyopathy, and valvar pulmonary stenosis. In patients with PLE, the T lymphocyte (CD3+) count was significantly lower (300 +/- 186 vs 2070 +/- 1171/microl, p = 0.017); both the helper/inducer lymphocytes (CD4+) (127 +/- 158 vs 927+/- 377/microl, p = 0.006) and suppressor/cytotoxic lymphocytes (CD8+) (129 +/- 49 vs 850 +/- 695/microl, p = 0.057) reduced with reversal of CD4(+)/CD8(+) ratio (0.81 +/- 0.68 1.64 +/- 0.89, p = 0.027). Furthermore, IgG level was significantly reduced (5.12 +/- 2.84 vs 12.5 +/- 1.58 g/L, p = 0.005) and IgA level tended to be lower (1.36 +/- 1.37 vs 2.50 +/- 0.80 g/L, p = 0.095). In contrast, the B lymphocyte (CD19+) count (340 +/- 151 vs 618 +/- 427/microl, p = 0.25), natural killer cell count (CD16(+) 56(+) CD3(-)) (252 +/- 212 vs 276 +/- 251/microl, p = 0.85), and IgM level (0.98 +/- 0.59 vs 1.12 +/- 0.25 g/L, p = 0.67) were similar for both groups. None of the patients developed opportunistic or severe viral infections. Abnormal immunologic profile of both the cellular and humoral arms of the immune system occurs in patients with congenital heart disease complicated by PLE. Nonetheless, these abnormalities perhaps appear quantitative rather than qualitative in nature, although further functional studies of antibody production and lymphocyte proliferation assays are required to support this proposition.