Grzegorz Porębski

The relationship between airborne pollen and fungal spore concentrations and seasonal pollen allergy symptoms in Cracow in 1997–1999

The investigation of airborne pollen and fungalspore concentrations was carried out in Cracowbetween 1997–1999. For this study thevolumetric method has been employed (Burkard).At the same time the clinical diagnosis ofpollen allergy in 40 patients was obtained onthe basis of an interview, positive skin pricktests with pollen extracts and increasedspecific IgE level. An increase in seasonalallergy symptoms in all patients occurred fromthe middle of May to the middle of August.Eighty eight percent of the patients (35 out of40) were sensitive to Poaceae pollen and about50% of them were additionally sensitive totree and herb pollen excluding grasses. Forpatients with additional allergy to tree pollenthe seasonal symptoms started at the end ofMarch (Betula) while for patients withadditional allergy to herb pollen it wasextended to the middle of September (Artemisia).Five people out of 40 revealed positive skinreactions to Alternaria spores and anincrease in specific IgE level. Positive skinreaction to Cladosporium spores with noincrease in specific IgE level occurred in 2patients. The increase in seasonal allergysymptoms in people sensitive to Alternariaspores noted in July and August could becaused not only by these spores but also byPoaceae pollen.

The prophylaxis of hereditary angioedema attacks with recombinant human C1 inhibitor: who will take advantage of the individualized treatment approach?

Replacement therapy, given intravenously, has been used for many years in the treatment of acute hereditary angioedema (HAE) attacks. Recently, the indications for long-term prophylaxis with plasma derived (pd) or recombinant human (rh) C1INH concentrate in HAE have been debated (1). Clearly, there is a need for more data on the benefit and safety of this therapy. The study by Reshef et al. (2) investigating rhC1INH in the prevention of HAE attacks is a welcome contribution to this evidence base. The authors have demonstrated that a weekly administration of 50 U/kg rhC1INH reduced the frequency of HAE attacks from a mean of 0.9 attacks/week in the past to the rate of 0.4 attacks/week during the treatment period, which corresponds to the avoidance of one attack per every 2 weeks, on average. There are some issues arising from this study that may be considered in more detail. Firstly, despite the fact that the overall average effect of intervention was positive, the response to rhC1INH differed one from another in individual cases. Four (16%) of the patients were symptom free during the treatment period, another two had a considerable decrease in the frequency of HAE attacks, but the others experienced only a moderate reduction in the occurrence of attacks. Similar observations were made in another study on replacement prophylactic therapy in HAE (3). This differentiation in patients’ response to treatment brings up questions (i) whether there is a possibility for an a priori identification of the best responders to investigated therapy (based on clinical features or the other biomarkers) and (ii) whether it would be helpful to use additional secondary end points, which would allow us to measure more precisely the clinical benefit from therapy for those patients who did not have a substantial decrease in the frequency of attacks (e.g., the severity and duration of attacks, the total number of days without swelling, the time to the onset of an unequivocal relief of the symptoms, or the need for hospitalization and rescue treatment due to lifethreatening symptoms). Secondly, the available data on a patient’s clinical course after there has been a discontinuation of the long-term prophylactic treatment with C1INH are limited and are usually not discussed widely in clinical trials. Here, the authors reported a serious adverse event (a fatal laryngeal edema, 25 days after the last administration of rhC1INH in the study). In another study, a tendency to develop more attacks during long-term prophylaxis with pdC1INH was observed (4). It would be of interest to practitioners and patients to know how, and to what extent, a discontinuation of prophylactic replacement therapy influences the severity and frequency of HAE attacks. It is certain that the safety of this treatment still requires further studies. Thirdly, the authors are absolutely right when they notice that intrapatient variation in a disease course over time can be significant (5, 6). If there is seen to be a great variance of the clinical expression of HAE in the same patient, this factor can obviously cause a potential bias in the assessment of the efficacy of the prophylactic treatment. Moreover, it seems that even an accurate recording of symptoms cannot overcome this limitation, especially in studies with a longterm observation period. Finally, efforts should also be made, in the future, to collect comprehensive information on a head-to-head comparison between the various existing prophylactic regimens, and on determination of what the most effective dose of prophylactic C1INH is required to optimize clinical response. As long as pointed questions remain unanswered, it is reasonable to limit the prophylaxis with rhC1INH only to highly selected patients with the most severe clinical course of HAE. A further extension of the number of patients for whom this treatment may be indicated needs to be based on convincing pieces of evidence that a considerable percentage of patients profit from this treatment. We should also take into account what prospect this treatment gives the patient of avoiding serious HAE attacks, how much effort is required of the patient, and, finally, how cost-effective the treatment is.

Serum Albumin Complexation of Acetylsalicylic Acid Metabolites

One possible origin of the type I hypersensitivity reaction is reaction of drugs such as acetylsalicylic acid and its metabolites being complexed with human serum albumin. Albumin, being transporting molecule abundant in blood plasma is able to bind large array of ligands varying from small single carbon particles to long hydrophobic tailed lipidic acids (e.g. myristic acid). This non specificity is possible because of multi domain scaffold and large flexibility of inter-domain loops, which results in serious reorientation of domains. Hypothesis that acetylsalicylic acid metabolites may play indirect role in activation of allergic reaction has been tested. Binding of acetylsalicylic acid metabolites in intra-domain space causes significant increase of liability of domains IIIA and IIIB. One of metabolites, salicyluric acid, once is bound causes distortion and partial unfolding of helices in domains IA, IIB and IIIB. Changed are both directions and amplitude of relative motions as well as intra-domain distances. In result albumin is able to cross-link of adjacent IgE receptors which subsequently starts allergic reaction.

Targeted next-generation sequencing for the molecular diagnosis of hereditary angioedema due to C1-inhibitor deficiency

SERPING1 genotyping of subjects suspicious for hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) is important for clinical practice as well as for research reasons. Conventional approaches towards the detection of C1-INH-HAE-associated SERPING1 variants are cumbersome and time-demanding with many pitfalls. To take advantage of the benefits of next-generation sequencing (NGS) technology, we developed and validated a custom NGS platform that, by targeting the entire SERPING1 gene, facilitates genetic testing of C1-INH-HAE patients in clinical practice. In total, 135 different C1-INH-HAE-associated SERPING1 variants, out of the approximately 450 reported, along with 115 negative controls and 95 randomly selected DNA samples from affected family members of C1-INH-HAE index patients, were included in the forward and reverse validation processes of this platform. Our platforms performance, i.e. analytical sensitivity of 98.96%, a false negative rate of 1.05%, analytical specificity 100%, a false positive rate equal to zero, accuracy of 99.35%, and repeatability of 100% recommends its implementation as a first line approach for the genetic testing of C1-INH-HAE patients or as a confirmatory method. A noteworthy advantage of our platform is the concomitant detection of single nucleotide variants and copy number variations throughout the whole length of the SERPING1 gene, moreover providing information about the size and the localization of the latter. During our study, 15 novel C1-INH-HAE-related SERPING1 variants were detected.

Management of suspected drug hypersensitivity reactions. Guidelines of the Section of Drug Hypersensitivity of the Polish Society of Allergology

1Klinika Immunologii, Reumatologii i Alergii, Uniwersytet Medyczny w Łodzi 2 Klinika Pulmonologii, II Katedra Chorób Wewnętrznych im. Prof. Andrzeja Szczeklika, Uniwersytet Jagielloński Collegium Medicum w Krakowie 3Klinika Alergologii i Chorób Wewnętrznych, Uniwersytet Medyczny w Białymstoku 4 Katedra i Klinika Chorób Wewnętrznych, Alergologii i Immunologii Klinicznej, Wydział Lekarski z Oddziałem Lekarsko-Dentystycznym w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach 5Zakład Alergologii Klinicznej, Pomorski Uniwersytet Medyczny w Szczecinie 6Katedra i Klinika Chorób Wewnętrznych i Alergologii, Uniwersytet Medyczny we Wrocławiu 7Zakład Alergologii Klinicznej i Środowiskowej, Uniwersytet Jagielloński Collegium Medicum w Krakowie 8Poradnia Alergologiczna i Poradnia Alergologiczna dla Dzieci w Starachowicach 9 Poradnia Alergologiczna, Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego w Szczecinie 10Klinika Reumatologii, Uniwersytet Medyczny w Łodzi

Introduction to management of drug hypersensitivity. Guidelines of the Section of Drug Hypersensitivity of the Polish Society of Allergology

1Klinika Immunologii, Reumatologii i Alergii, Uniwersytet Medyczny w Łodzi 2 Klinika Pulmonologii, II Katedra Chorób Wewnętrznych im. Prof. Andrzeja Szczeklika, Uniwersytet Jagielloński Collegium Medicum w Krakowie 3Klinika Alergologii i Chorób Wewnętrznych, Uniwersytet Medyczny w Białymstoku 4 Katedra i Klinika Chorób Wewnętrznych, Alergologii i Immunologii Klinicznej, Wydział Lekarski z Oddziałem Lekarsko-Dentystycznym w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach 5Zakład Alergologii Klinicznej, Pomorski Uniwersytet Medyczny w Szczecinie 6Katedra i Klinika Chorób Wewnętrznych i Alergologii, Uniwersytet Medyczny we Wrocławiu 7Zakład Alergologii Klinicznej i Środowiskowej, Uniwersytet Jagielloński Collegium Medicum w Krakowie 8Poradnia Alergologiczna i Poradnia Alergologiczna dla Dzieci w Starachowicach 9 Poradnia Alergologiczna, Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego w Szczecinie 10Klinika Reumatologii, Uniwersytet Medyczny w Łodzi

Hypersensitivity to nonsteroidal anti-inflammatory drugs. Guidelines of the Section of Drug Hypersensitivity of the Polish Society of Allergology

1Katedra i Klinika Chorób Wewnętrznych i Alergologii, Uniwersytet Medyczny we Wrocławiu 2 Klinika Pulmonologii, II Katedra Chorób Wewnętrznych im. Prof. Andrzeja Szczeklika, Uniwersytet Jagielloński Collegium Medicum w Krakowie 3Klinika Alergologii i Chorób Wewnętrznych, Uniwersytet Medyczny w Białymstoku 4 Katedra i Klinika Chorób Wewnętrznych, Alergologii i Immunologii Klinicznej, Wydział Lekarski z Oddziałem Lekarsko-Dentystycznym w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach 5Klinika Immunologii, Reumatologii i Alergii, Uniwersytet Medyczny w Łodzi 6Zakład Alergologii Klinicznej i Środowiskowej, Uniwersytet Jagielloński Collegium Medicum w Krakowie 7Poradnia Alergologiczna i Poradnia Alergologiczna dla Dzieci w Starachowicach 8Klinika Reumatologii, Uniwersytet Medyczny w Łodzi

Drug-specific in vitro release of IFN-gamma in patients with delayed cutaneuos drug hypersensitivity reactions

Method A total of 16 patients with clinically well-established maculopapular exanthema due to antiepileptic drugs hypersensitivity in remission state and 15 drug-exposed control donors without DHR were included to the study. Peripheral blood mononuclear cells of investigated individuals were isolated and cultured under defined conditions with drugs. IFN-gamma production was measured with electrochemiluminescence array assay and ELISA (cytokine level in cell culture supernatant), ELISpot (cytokine secreting cells), flow cytometry (intracellular staining in CD3+ CD4+ cells).

Cytotoxic diagnostic assays are effective in drug-induced maculopapular exanthemas

Background Cytotoxic mechanisms are involved in most forms of drug-induced skin diseases, but till now only a small number of studies has been addressed the question whether in vitro detection of cytotoxic drug-specific response could be helpful in drug hypersensitivity diagnosis. The aim of this study was to assess and compare different cytotoxic tests as an alternative nonradioactive approach which may be more appropriate for routine testing and may provide in addition more information about the pathophysiology of the reaction than proliferation-based assays, like the lymphocyte transformation test (LTT).