Unexpectedly High Prevalence of Common Variable Immunodeficiency in Finland

Background: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. Prevalence varies greatly between countries and studies. Most diagnostic criteria include hypogammaglobulinemia and impaired vaccine response. Aim: To evaluate the minimum prevalence as well as the clinical and immunological phenotypes of CVID in Southern Finland. Methods: We performed a cross-sectional study to assess all adult CVID patients followed up in three hospital districts in Southern and South-Eastern Finland between April 2007 and August 2015. CVID diagnosis was based, with a minor modification, on the ESID/PAGID criteria for primary CVID. Antipolysaccharide responses to Pneumovax (R) were defined as impaired only if 50% or more of the serotypes did not reach a level of 0.35 mu g/mL after vaccination. We further characterized the patients' B cell phenotypes and complications associated with CVID. Results: In total, 9 patients were excluded due to potential secondary causes before diagnosis. ESID/PAGID criteria were met by 132 patients (males 52%), of whom, 106 had "probable" and 26 "possible CVID." Based on the population statistics in the three hospital districts, the minimum adult prevalence per 100,000 inhabitants in Finland for all CVID ("probable CVID," respectively) patients was 6.9 (5.5). In the highest prevalence district (Helsinki and Uusimaa), the prevalence was 7.7 (6.1). CVID patients suffer from frequent complications. Ten patients died during follow-up. Of probable CVID patients, 73% had more than one clinical phenotype. Intriguingly, gradual B cell loss from peripheral blood during follow-up was seen in as many as 16% of "Xprobable CVID" patients. Patients with possible CVID displayed somewhat milder clinical and laboratory phenotypes than probable CVID patients. We also confirm that large granular lymphocyte lymphoproliferation is a CVID-associated complication. Conclusion: The prevalence of CVID in Finland appears the highest recorded, likely reflecting the genetic isolation and potential founder effects in the Finnish population. Studies to discover potential gene variants responsible for the high prevalence in Finland thus seem warranted. Increased awareness of CVID among physicians would likely lead to earlier diagnosis and improved quality of care.Peer reviewe

Dirofilaria repens transmission in southeastern Finland

Background: The spread of vector-borne diseases to new regions has become a global threat due to climate change, increasing traffic, and movement of people and animals. Dirofilaria repens, the canine subcutaneous filarioid nematode, has expanded its distribution range northward during the last decades. The northernmost European locations, where the parasite life-cycle has been confirmed, are Estonia and the Novgorod Region in Russia. Results: Herein, we describe an autochthonous D. repens infection in a Finnish woman. We also present two cases of D. repens infection in imported dogs indicating the life-cycle in the Russian Vyborg and St Petersburg areas, close to the Finnish border. Conclusions: The most obvious limiting factor of the northern distribution of D. repens is the summer temperature, due to the temperature-dependent development of larvae in vectors. With continuing climate change, further spread of D. repens in Fennoscandia can be expected.Peer reviewe

Se-77 NMR spectroscopic, DFT MO, and VBT investigations of the reversible dissociation of solid (Se6I2)[AsF6](2)center dot 2SO(2) in liquid SO2 to solutions containing 1,4-Se6I22+ in equilibrium with Se-n(2+) (n=4, 8, 10) and seven binary selenium iodine cations: preliminary evidence for 1,1,4,4-Se4Br42+ and cyclo-Se7Br+

The composition of a complex equilibrium mixture formed upon dissolution of (Se6I2)[AsF6](2)center dot 2SO(2) in SO2(l) was studied by Se-77 NMR spectroscopy at -70 degrees C with both natural-abundance and enriched Se-77-isotope samples (enrichment 92%). Both the natural-abundance and enriched NMR spectra showed the presence of previously known cations 1,4-Se6I22+, SeI3+, 1,1,4,4-Se4I42+ Se-10(2+), Se-8(2+), and Se-4(2+). The structure and bonding in 1,4-Se6I22+ and 1,1,4,4-Se4I42+ were explored using DFT calculations. It was shown that the observed Se-Se bond alternation and presence of thermodynamically stable 4p pi-4p pi Se-Se and 4p pi-5p pi Se-I bonds arise from positive charge delocalization from the formally positively charged tricoordinate Se+. The Se-77 chemical shifts for cations were calculated using the relativistic zeroth-order regular approximation (ZORA). In addition, calculations adding a small number of explicit solvent molecules and an implicit conductor-like screening model were conducted to include the effect that solvent has on the chemical shifts. The calculations yielded reasonable agreement with experimental chemical shifts, and inclusion of solvent effects was shown to improve the agreement over vacuum values. The Se-77 NMR spectrum of the equilibrium solution showed 22 additional resonances. These were assigned on the basis of Se-77-Se-77 correlation spectroscopy, selective irradiation experiments, and spectral simulation. By combining this information with the trends in the chemical shifts, with iodine, selenium, and charge balances, as well as with ZORA chemical shift predictions, these resonances were assigned to acyclic 1,1,2-Se2I3+, 1,1,6,6-Se6I42+, and 1,1,6-Se6I3+, as well as to cyclic Se7I+ and (4-Se7I)(2)I3+. A preliminary natural-abundance Se-77 NMR study of the soluble products of the reaction of (Se-4)[AsF6](2) and bromine in liquid SO2 included resonances attributable to 1,1,4,4-Se4Br42+. These assignments are supported by the agreement of the observed and calculated 77Se chemical shifts. Resonances attributable to cyclic Se7Br+ were also observed. The thermal stability of (Se6I2)[AsF6](2)center dot 2SO(2)(S) was consistent with estimates of thermodynamic values obtained using volume-based thermodynamics (VBT) and the first application of the thermodynamic solvate difference rule for nonaqueous solvates. (Se6I2)[AsF6](2)center dot 2SO(2)(s) is the first example of a SO2 solvate for which the nonsolvated parent salt, (Se6I2)[AsF6](2)(s), is not thermodynamically stable, disproportionating to Se4I4(AsF6)(2)(s) and Se-8(AsF6)(2)(S) (Delta G degrees for the disproportion reaction is estimated to be -17 +/- 15 kJ mol(-1) at 298 K from VBT theory)