Protection or susceptibility to devastating childhood epilepsy: Nodding Syndrome associates with immunogenetic fingerprints in the HLA binding groove.

Nodding syndrome (NS) is a devastating and enigmatic childhood epilepsy. NS is accompanied by multiple neurological impairments and neuroinflammation, and associated with the parasite Onchocerca volvulus (Ov) and other environmental factors. Moreover, NS seems to be an 'Autoimmune Epilepsy' since: 1. ~50% of NS patients have neurotoxic cross-reactive Ov/Leimodin-I autoimmune antibodies. 2. Our recently published findings: Most (~86%) of NS patients have glutamate-receptor AMPA-GluR3B peptide autoimmune antibodies that bind, induce Reactive Oxygen Species, and kill both neural cells and T cells. Furthermore, NS patient's IgG induce seizures, brain multiple damage alike occurring in brains of NS patients, and elevation of T cells and activated microglia and astrocytes, in brains of normal mice. Human Leukocyte antigen (HLA) class I and II molecules are critical for initiating effective beneficial immunity against foreign microorganisms and contributing to proper brain function, but also predispose to detrimental autoimmunity against self-peptides. We analyzed seven HLA loci, either by next-generation-sequencing or Sequence-Specific-Oligonucleotide-Probe, in 48 NS patients and 51 healthy controls from South Sudan. We discovered that NS associates significantly with both protective HLA haplotype: HLA-B*42:01, C*17:01, DRB1*03:02, DQB1*04:02 and DQA1*04:01, and susceptible motif: Ala24, Glu63 and Phe67, in the HLA-B peptide-binding groove. These amino acids create a hydrophobic and sterically closed peptide-binding HLA pocket, favoring proline residue. Our findings suggest that immunogenetic fingerprints in HLA peptide-binding grooves tentatively associate with protection or susceptibility to NS. Accordingly, different HLA molecules may explain why under similar environmental factors, only some children, within the same families, tribes and districts, develop NS, while others do not.

Splenectomy during secondary cytoreduction for ovarian cancer disease recurrence: surgical and survival data.

BACKGROUND: Ovarian cancer disease recurs predominantly in the abdomen, with the spleen usually involved as part of a vast spread of upper-abdominal disease or, less frequently, as an isolated site of disease recurrence. Very few reports are available in the literature on the outcome of patients subjected to splenectomy during secondary cytoreduction. The aim of this study was to identify prognostic factors and to review surgical and clinical data in order to identify those patients who would benefit the most from splenectomy during secondary cytoreduction. METHODS: This was a retrospective review of platinum-sensitive recurrent epithelial ovarian cancer patients who underwent splenectomy as part of secondary cytoreduction. Surgical and survival data were recorded. RESULTS: Twenty-four patients were identified. Multiple site disease recurrence was observed in 15 patients. The spleen was involved at the hilus in 12 patients; surface and intraparenchymal metastases were equally present. Optimal cytoreduction was achieved in all patients. At a median follow-up of 30 months, median progression-free and overall survival from the time of secondary surgery were 34 and 56 months, respectively. Overall survival was significantly correlated to residual disease at secondary surgery, disease-free survival, consolidation chemotherapy, and type of adjuvant therapy. CONCLUSIONS: Splenectomy as part of secondary cytoreduction is a feasible and safe procedure. Secondary cytoreduction in selected groups of patients is confirmed to be associated with high long-term survival rates even when aggressive surgery of the upper abdomen is required.