title: Gene expression profiling in cluster headache: a pilot microarray study.
abstract: BACKGROUND
  Cluster headache (CH) is a primary neurovascular headache disorder characterized by attacks of excruciating pain accompanied by ipsilateral autonomic symptoms. CH pathophysiology is presumed to involve an activation of hypothalamic and trigeminovascular systems, but inflammation and immunological mechanisms have also been hypothesized to be of importance.
  
  
  OBJECTIVE
  To identify differentially expressed genes during different clinical phases of CH, assuming that changes of pathophysiological importance would also be seen in peripheral venous blood.
  
  
  METHODS
  Blood samples were drawn at 3 consecutive occasions from 3 episodic CH patients: during attacks, between attacks and in remission, and at 1 occasion from 3 matched controls. Global gene expression was analyzed with microarray tehnology using the Affymetrix Human Genome U133 2.0 Plus GeneChip Set, covering more than 54,000 gene transcripts, corresponding to almost 22,000 genes. Quantitative RT-PCR on S100P gene expression was analyzed in 6 patients and 14 controls.
  
  
  RESULTS
  Overall, quite small differences were seen intraindividually and large differences interindividually. However, pairwise comparisons of signal values showed upregulation of several S100 calcium binding proteins; S100A8 (calgranulin A), S100A12 (calgranulin C), and S100P during active phase of the disease compared to remission. Also, annexin A3 (calcium-binding) and ICAM3 showed upregulation. BIRC1 (neuronal apoptosis inhibitory protein), CREB5, HLA-DQA1, and HLA-DQB1 were upregulated in patients compared to controls. The upregulation of S100P during attack versus remission was confirmed by quantitative RT-PCR analysis.
  
  
  CONCLUSIONS
  The S100A8 and S100A12 proteins are considered markers of non-infectious inflammatory disease, while the function of S100P is still largely unknown. Furthermore, upregulation of HLA-DQ genes in CH patients may also indicate an inflammatory response. Upregulation of these pro-inflammatory genes during the active phase of CH has not formerly been reported. Data from this pilot microarray study provide a basis for further studies in CH.
authors.affiliation: Clinical Neuroscience--Neurology, Karolinska University Hospital, Huddinge, 14186 Stockholm, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Sjöstrand
authors.forename: Kristina
authors.initials: K
authors.lastname: Duvefelt
authors.forename: Anna
authors.initials: A
authors.lastname: Steinberg
authors.forename: Ingela Nilsson
authors.initials: IN
authors.lastname: Remahl
authors.forename: Elisabet
authors.initials: E
authors.lastname: Waldenlind
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
mesh_terms: D000328:Adult; D003027:Cluster Headache / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012313:RNA