Elif Karakoc Aydıner, Turkey
Marmara University Department of Pediatric Allergy and ImmunologyPresenter of 2 Presentations
TREATMENT OF CHAPLE DISEASE WITH THE COMPLEMENT INHIBITOR ECULIZUMAB
Abstract
Background and Aims
We have recently demonstrated that early-onset Waldmann’s protein-losing enteropathy can be caused by CD55 mutations and established the pathogenic role of complement activation in intestinal lymphangiectasia and severe thromboses (CHAPLE syndrome). We sought to evaluate the therapeutic efficacy of eculizumab, a monoclonal antibody against C5 in CHAPLE patients and investigate the molecular signatures and potential biomarkers.
Methods
Fifteen patients with CHAPLE syndrome received eculizumab for a mean of 12.3 months and were carefully monitored for effects on disease and adverse events. Outcome parameters included clinical symptoms, blood chemistry, nutrition, quality of life scores, structural gastrointestinal abnormalities, and malabsorption indices. SOMALogic assay investigated pathological serum signatures of CHAPLE syndrome and their dynamic changes in response to therapy.
Results
Eculizumab provided an immediate effect in all patients, with a gradual increase in total protein, albumin and immunoglobulin levels, which are completely restored within 4 weeks. Symptom diaries demonstrated a significant decrease in the scores of nausea, vomiting, abdominal pain and facial edema, and reduced number of bowel movements. Eculizumab reversed hematological abnormalities and intestinal malabsorption and led to a significant improvement in growth indices and overall health outcomes over time. Importantly, life threatening complications of CHAPLE syndrome were ameliorated, and patients were able to discontinue prior medications including those which were associated with significant adverse effects. Unintentional discontinuation of eculizumab longer than 6 weeks led to a relapse of symptoms. We detected major alterations in numerous biomolecules in the serum samples.
Conclusions
Eculizumab proved safe and highly effective in CHAPLE syndrome.
MALIGNANCY IN ATAXIA-TELANGIECTASIA PATIENTS: MARMARA EXPERIENCE
Abstract
Background and Aims
Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterised by neurodegenerative symptoms, skin manifestations, immune deficiency and increased susceptibility to cancer.
Methods
27AT(16F/11M) patients were collected for their demographic, clinical and laboratory data.
Results
27 patients were diagnosed with ataxia telangiectasia according to ESID registry diagnostic criteria. The current mean age was 10.9±6,3 years. Seventeen (60.7%) of patients were female, 11(39.3%) were male. The mean age at diagnosis was 3.5±3 years. Nine (33.3%) patients were on IVIG replacement therapy, 11 (%40.7) received antibiotic prophylaxis. Median absolute lymphocyte count (ALC) of patients was 1900/mm3(600-9800). Immunoglobulin levels were as follows: low IgG in 3 (%12), normal IgG in 19 (%76) and elevated in 3(%12), low IgA in 22 (%88), low IgM in 1 patient, normal IgM in 19(%76) and elevated IgM in 5(%20). Malignancy developed in 2 (7.4%) of the patients. One of the female patients diagnosed with disgerminoma at age of 17, the other was diagnosed with T cell lymphoma at age of 5. One mother of AT patient developed breast cancer and was treated accordingly.
| IgG(mg/dl) | 1230(94-2250) |
| IgA(mg/dl) | 11,5(5-199) |
| IgM(mg/dl) | 249(20-1060) |
| AFP(mg/dl) | 111(26,7-721) |
| ALC(#/mm3) | 1900(600-9800) |
| ANC(#/mm3) | 3600(500-10700) |
| CD3% | 54,8(15-82) |
| CD3(#/mm3) | 1032(263-6860) |
| CD3CD4% | 28(3-52) |
| CD3CD4(#/mm3) | 499(115-5096) |
| CD3CD8% | 22,1(9-42,4) |
| CD3CD8 (#/mm3) | 446(87-1666) |
| CD19% | 5,2(0,3-59) |
| RTE% | 7,9(0,3-59) |
Conclusions
Ataxia-telangiectasia is a complex DNA repair disease, causing various clinical phenotypes, immune deficiency, malignancies, hypotonia and ataxia. Some patients may even be diagnosed with immunological abnormalities before the progression of neurological symptoms. AT patients and parents should be regularly monitored for malignancy development in the follow-up.