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Genetic studies associated certain N- glycosyltransferase loci with type 1 diabetes development. However, individual variation in plasma N-glycosylation has mostly been studied in the context of diabetes complications, and its role in type 1 diabetes onset is mainly unknown. In this study the aim was to explore N-glycome and genome interplay at the onset of type 1 diabetes. Plasma protein and IgG N-glycans were chromatographically analysed in a study population comprising 1917 children and adolescents (0.6-19.1 years) with recent-onset type 1 diabetes from the DanDiabKids registry. In the follow-up study results for 188 of these participants were compared with those for their 244 unaffected siblings. A total of 1105 new-onset type 1 diabetes patients were genotyped at 183, 546 genetic markers, testing these for genetic association with 24 IgG and 39 plasma protein N- glycans. Significant genetic associations were validated in 455 samples. Our study showed that onset of type 1 diabetes was characterised by an increase in plasma and IgG high-mannose and bisecting GlcNAc structures, a decrease in monogalactosylation, and an increase in IgG disialylation. Models including age, gender and N- glycans yielded significant discriminative power between children with type 1 diabetes and their unaffected siblings, with AUCs of 0.915 and 0.869 for inclusion of plasma and IgG N-glycans, respectively. This study identified novel associations that were not previously reported for the general European population: 1) novel genetic associations of IgG glycans were identified for SNPs on chromosome 22 close to candidate gene MGAT3 ; these include core fucosylated digalactosylated disialylated IgG N-glycan with bisecting GlcNAc and its asialylated version ; 2) novel genetic locus was associated with plasma protein N-glycosylation, the complement C3 gene (C3). C3 variants reside on chromosome 19 within the protein coding region, and the associated high-mannose Man9 glycan is attached on a domain involved in pathogen binding of the complement component C3, whereas identified C3 variants are often co-inherited with another type 1 diabetes risk-associated variant. This study identified distinct N-glycosylation of plasma proteins and IgG at type 1 diabetes onset, novel genetic variants driving these changes and potential underlying molecular mechanisms, which are still unknown for many identified type 1 diabetes risk- associated variants.

Onychomycosis is a significant public health problem in Croatia that affects about 4% of the general population and accounts for about 50% of all nail diseases. The disease affects one or more nails, and more often affects the toenails than the fingernails. The most common causes of onychomycosis are dermatophytes, non-dermatophyte hyaline moulds (NDM) and yeasts. We conducted a pilot study (from March to August 2021) to: i) determine sample size and potential risk factors related to onychomycoses of Croatian adult population (power analysis) ; ii) to explore dermatophyte diversity by combining standard microscopy (KOH solution) and cultivation (Sabouraud agar-SGA) with ITS sequence-based method. The pilot study included 112 subjects ; 91 were patients (67 women and 24 men) and 21 control subjects (17 women and 5 men). All respondents voluntarily participated in the anonymous study with informed consent and completion of the survey. Power analysis has shown that onychomycosis may be significantly affected by age, sports such as swimming and rowing, autoimmune diseases, the use of corticosteroids and dermatitis. Among patients, 43 positive results were obtained by direct microscopy with KOH. 59 isolates were identified by cultivation on SGA, of which 5 Candida sp., 40 NDM and 14 dermatophytes including Trichophyton rubrum (N=5), T. mentagrophytes (N=3), T. Interdigitale (N=4) and Microsporum canis (N=2). ITS sequencing revealed 5 isolates of T. rubrum and 1 isolate T. raubitschekii, a variant of T. rubrum ; 1 isolate of T. mentagrophytes and 5 isoaltes of Arthroderma vanbreuseghemii ; 1 isoalte of M. canis and 1 isolate of A. gypseum. Dermatophyte-positive samples were equally distributed among men and women. In the control group, 3 microscopic slides were tested positive, and all cultures remained negative. All samples in which dermatophytes were isolated were obtained from toenail samples, while Candida sp. and NDM are more often isolated from fingernail samples. In conclusion, the ITS sequencing method enables the differentiation of related dermatophyte species that cannot be determined by standard mycological cultivation methods, which makes it a valuable and less time-consuming diagnostic tool. The results are the basis for conducting a broader epidemiological study on the prevalence and species diversity of dermatophytes in onychomycosis in different counties of Croatia.

Recreational SCUBA (rSCUBA) diving is a specific type of underwater activity preformed in extreme environmental conditions. However, information on molecular events underlying (patho)physiological events that follow exposure to such conditions is still largely unexplored. To contribute to better understanding cardiac and immune system adaptation mechanisms triggered by repeated rSCUBA diving we measured copeptin, IgA, IgG, and IgM, complement components C3 and C4, and differential blood count parameters, including neutrophil­to­lymphocyte ratio (NLR), N­glycosylation of IgG and total plasma proteins (TPP), as well as cell­free DNA in blood samples of fourteen recreational male divers who performed five dives, one per week, on the depth 20­30 m for 30 min, after non­dive period of 5 months. Changes in measured parameters suggested that first dive triggered stress response that was abolished with repetition of diving since its beneficial effects on cardiac system (copeptin level) and immune status (NLR, immunoglobulins level, as well as IgG and TPP N­glycosylation pattern towards anti­inflammatory status) were observed after the following dives. In conclusion, rSCUBA diving practiced on a regular basis induce cardiac adaptive response and promotes anti­ inflammatory status of the organism thus conferring cardioprotection as well as multiple health benefits.

Glycosylation is present in all living organisms, ranging from bacteria and archaea all the way to humans. Glycan structures attached to lipids and proteins are not coded into the genome but are precisely added by enzymes involved in the glycosylation process. The observed increase in glycan structure complexity through evolution suggests that the glycosylation processes are under continuous evolutionary change. To reconstruct the evolutionary origin of the genes involved in N-glycosylation and their target proteins in H. sapiens we applied the phylostratigraphic approach. Results showed that homologs of most human genes involved in N- glycosylation could be traced back to the last universal common ancestor (LUCA) suggesting that the protein glycosylation is essential to all cellular life. Apart from that, we observed significant enrichment in the last eukaryotic common ancestor (LECA), probably linked to the emergence of the endomembrane system which plays important role in eukaryotic N-glycosylation. Focusing on the enzymes of the N-glycosylation biosynthetic pathway localized on the cytosolic and luminal side of the membrane of the endoplasmic reticulum, it has been observed that these enzymes are grouped into blocks and that evolutionarily older enzymes, originated in LUCA, are oriented toward the cytosolic side, while evolutionarily newer enzymes, originated in LECA, are oriented towards the lumen of the endoplasmic reticulum. Such rearrangement supports suggested theories of eukaryogenesis which theorize the development of the endomembrane system from the cell membrane of the host cell.

Introduction: IgA vasculitis (IgAV) is usually self-limiting with a favorable prognosis. However, the development of nephritis (IgAVN) can lead to chronic kidney disease and kidney biopsy has been a continued standard in determining the severity of IgAVN. The association between the disease activity, as well as laboratory parameters descibing kidney function, and different histologic classifications used for IgAVN are still left unclear. Objectives: To determine whether there is an association between histologic variables, measures of disease activity (PVAS) and markers of kidney function. Methods: Patients included were diagnosed with IgAV and IgAVN based on EULAR/PRINTO/PRES criteria in the period from 2003 to 2021. Their renal biopsy findings were examined using light microscopy, immunofluorescence, and electron microscopy analyses. Four classifications were used: ISKDC, Haas classification, Oxford classification, and SQC classification. PVAS was determined at the time of diagnosis. Results: The study included 67 patients, with the median (range) age of 10.8 (3.1-28.5) years at the diagnosis. Fifty-eight percent of patients were male, with a male to female ratio of 1.4:1. The median time from IgAV diagnosis to IgAV nephritis was 5 (0-270) days. The median time from the onset of nephritis to kidney biopsy was 30 (2-2555) days. Laboratory parameters were tested for association with all four classifications. Twenty- four hours protein excretion has shown statistically significant correlation with higher grade in Oxford classification (b= 0.58 ± 0.12, p

Genetic studies associated certain N- glycosyltransferase loci with type 1 diabetes development. However, individual variation in plasma N-glycosylation has mostly been studied in the context of diabetes complications, and its role in type 1 diabetes onset is mainly unknown. In this study the aim was to explore N-glycome and genome interplay at the onset of type 1 diabetes. Plasma protein and IgG N-glycans were chromatographically analysed in a study population comprising 1917 children and adolescents (0.6-19.1 years) with recent-onset type 1 diabetes from the DanDiabKids registry. In the follow-up study results for 188 of these participants were compared with those for their 244 unaffected siblings. A total of 1105 new-onset type 1 diabetes patients were genotyped at 183, 546 genetic markers, testing these for genetic association with 24 IgG and 39 plasma protein N- glycans. Significant genetic associations were validated in 455 samples. Our study showed that onset of type 1 diabetes was characterised by an increase in plasma and IgG high-mannose and bisecting GlcNAc structures, a decrease in monogalactosylation, and an increase in IgG disialylation. Models including age, gender and N- glycans yielded significant discriminative power between children with type 1 diabetes and their unaffected siblings, with AUCs of 0.915 and 0.869 for inclusion of plasma and IgG N-glycans, respectively. This study identified novel associations that were not previously reported for the general European population: 1) novel genetic associations of IgG glycans were identified for SNPs on chromosome 22 close to candidate gene MGAT3 ; these include core fucosylated digalactosylated disialylated IgG N-glycan with bisecting GlcNAc and its asialylated version ; 2) novel genetic locus was associated with plasma protein N-glycosylation, the complement C3 gene (C3). C3 variants reside on chromosome 19 within the protein coding region, and the associated high-mannose Man9 glycan is attached on a domain involved in pathogen binding of the complement component C3, whereas identified C3 variants are often co-inherited with another type 1 diabetes risk-associated variant. This study identified distinct N-glycosylation of plasma proteins and IgG at type 1 diabetes onset, novel genetic variants driving these changes and potential underlying molecular mechanisms, which are still unknown for many identified type 1 diabetes risk- associated variants.

Thallium is a naturally occurring, highly toxic trace element. Human exposure to thallium is mainly connected to occupational exposure, environmental contamination and food accumulation. The exact mechanism of thallium toxicity is still poorly understood, however its toxic effect is often connected to disruption of potassium-dependent processes and development of oxidative stress. The aim of this study was to access the cytotoxic effect of thallium on several cell culture lines and relate the obtained results with its specific toxicity to a particular organ. In addition, possible protective effect of potassium on toxicity of thallium was also examined. Human keratinocytes (HaCaT), human hepatocellular carcinoma (HepG2), porcine kidney epithelial cells (PK15), human neuroblastoma (SH-SY5Y) and Chinese hamster lung fibroblast cells (V79) were treated with thallium (I) acetate in a wide concentration range (3.9-500 µg/ml) for 24h, 48h and 72h. Based on cytotoxicity results, four concentrations (15.6, 31.25, 62.5, 125 µg/ml) were chosen to be tested in combination with potassium acetate (500 μg/ml) to assess their competitive interaction during 24h treatment. Cell morphological changes were monitored on inverted microscope, and cytotoxic effect was assessed by 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide (MTT-test). Thallium toxicity for each cell line tested was both, time- and dose-dependent. For each measurement point SH-SY5Y cells had the lowest IC50 values and appeared to be most sensitive, while HepG2 were most resistant to thallium exposure. Simultaneous treatment of cells with thallium and potassium (I) acetate resulted with higher viability compared to treatment with thallium (I) acetate alone. Results of our study indicate that tissue origin contributes to cell’s susceptibility to thallium toxicity. Different toxic effect of thallium could be attributed to cell’s antioxidant capacity as well as transport systems through which thallium and potassium compete for entering the cell. The obtained results point to importance of monitoring thallium concentrations in the environment and call for further research into the mechanism of its toxicity.

Uvod. Sindrom aktivacije makrofaga (MAS) ozbiljna je komplikacija sistemskih upalnih poremećaja, koji se najčešće javlja u sistemskom tipu juvenilnog idiopatskog artritisa (sJIA). Disfunkcionalni imuni odgovor dovodi do pretjerane upalne reakcije uzrokujući hipersekreciju proinflamatornih citokina koja može biti životno ugrožavajuća. Ispitanici i metode. Retrospektivno su prikupljeni podaci djece oboljele od sJIA Referentnog centra za pedijatrijsku i adolescentnu reumatologiju. Laboratorijski podaci su prikupljeni na početku hospitalizacije (T1) i prije uvođenja imunosupresivne terapije (T2), tada bez simptoma MAS-a prema kriterijima EULAR/ACR/PRINTO iz 2016.g. Bolesnici su podijeljeni u dvije skupine, ovisno o tome jesu li ili nisu razvili MAS tijekom daljnjeg tijeka bolesti. Analizirani su feritin, AST, ALT gGT, LDH, trigliceridi, fibrinogen, D-dimeri, CRP, hemoglobin, broj leukocita, neutrofila i trombocita. Rezultati. Analizirali smo laboratorijske podatke 32 bolesnika, od kojih je 5 razvilo sindrom aktivacije makrofaga. 59% bolesnika je bilo muškog spola, bez razlike u spolu nakon podjele u dvije skupine. Medijan (raspon) dobi bolesnika s MAS-om je bio 1, 24 (1, 2–16, 9) godina, a bez MAS-a 10, 6 (0, 87–17, 4) godina. Na početku hospitalizacije nije bilo razlike u laboratorijskim podacima između bolesnika kojisu kasnije razvili MAS i onih koji nisu. Razine feritina bile su statistički značajno više u drugom mjerenju prije uvođenja imunosupresivne terapije kod bolesnika koji su kasnije razvili MAS (p = 0, 003, medijan 3411, 8 ug/Lvs 314, 35ug/L), kao i razine AST-a (p = 0, 014, medijan 67 UI/Lvs 27 UI/L). Hemoglobin je bio značajno niži u skupini koja je kasnije razvila MAS (p = 0, 022, medijan 90 g/Lvs 105 g/L). Pri analizi same veličine promjene laboratorijskih nalaza od T1 do T2 između dviju grupa nije uočena značajna razlika. Zaključak. Feritin, AST i hemoglobin pokazali su se značajnima u bolesnika koji su razvili MAS te bi mogli imati ulogu predskazatelja onih oboljelih od sJIA kojima prijeti razvoj MAS-a. Veće istraživanje je potrebno kako bi se istražila mogućnost primjene ovih laboratorijskih parametara i njihove točne vrijednosti kao predskazatelja MAS-a.

Talij je jedan od najtoksičnijih kemijskih elemenata [1]. Ion talija (Tl+) ima atomski radijus približno jednak radijusu iona kalija (K+) te se pretpostavlja da talij ulazi u stanicu pomoću Na+/K+ ATP-aze [2]. U ovom je istraživanju ispitan protektivni učinak kalija na toksičnost talija tako što je pet staničnih linija (HepG2, HaCaT, pk15, SH-SY5Y i V79) tretirano s talijevim (I) acetatom (koncentracijski raspon: 15, 6 do 125 μg/ml, 24 h) ili s talijevim (I) acetatom (koncentracijski raspon: 15, 6 do 125 μg/ml, 24 h) zajedno s kalijevim (I) acetatatom (500 μg/ml, 24 h) te je praćena vijabilnost stanica MTT testom. Dobiveni rezultati citotoksičnosti statistički su uspoređeni višestrukim t-testovima (korekcija po Benjamini-Hochbergu) te modelom mješovitih efekata analize varijance (ANOVA). Talij je bio citotoksičan za sve stanične linije, a njegova citotoksičnost bila je ovisna o koncentraciji. U odnosu na tretman s talijem i kalijem zajedno, tretman samo s talijem bio je toksičniji za sve stanične linije. Nakon zajedničkog tretmana s talijem i kalijem zabilježena je statistički značajno niža citotoksičnost u odnosu na tretman samo s talijem kod svih staničnih linija osim kod V79 stanične linije. Rezultati istraživanja upućuju da kalij može spriječiti citotoksični učinak talija, što potvrđuje pretpostavku da Tl+ koristi membranske proteine K+ za ulazak u stanicu.

Introduction Several histologic classifications are used in the evaluation of IgA vasculitis nephritis (IgAVN), however, to date, no studies have determined which one has the strongest association with the severity of IgAVN and, as a consequence, its outcomes. Materials and methods Patients included in the study were diagnosed with IgAV and IgAVN in seven tertiary university medical centers in Croatia, Italy and Israel. The International Study of Kidney Disease in Children (ISKDC), Haas, Oxford, and Software Quality Control (SQC) classifications were used in the analysis and description of renal biopsy. Time from biopsy to outcome evaluation was a statistically significant factor in outcome prediction that was used to define the base model, and was a covariate in all the tested models. Results Sixty-seven patients were included in this study. The SQC classification proved to be the best one in outcome prediction, followed by the Oxford classification. The ISKDC and Haas classifications could not predict renal outcome. The Oxford parameters for mesangial hypercellularity and tubular atrophy, as well as the SQC parameters for cellular crescents showed an independent statistically significant contribution to outcome prediction. High level of twenty-four hour protein excretion was associated with a higher grade in the Oxford, SQC and ISKDC classifications. Endocapillary proliferation was positively associated with the Pediatric Vasculitis Activity Score (PVAS) at diagnosis, while tubular atrophy was negatively associated. Conclusion The SQC, followed by the Oxford classification were found to provide the best classifications of renal biopsy analysis in patients to predict the outcome in patients with IgAVN. Cellular crescents, mesangial hypercellularity and tubular atrophy showed significant contributions, indicating that active and chronic variables should be included in the estimation.

Uloga N-glikozilacije proteina plazme u nastanku šećerne bolesti tipa 1 je neistražena. Ovo istraživanje uključilo je 1917 djece čiji su uzorci krvne plazme prikupljeni pri početku šećerne bolesti tipa 1 kroz DanDiabKids registar, kao i 265 zdravih srodnika. N-glikani proteina plazme analizirani su tekućinskom kromatografijom, dok je genotipizacija ispitanika provedena pomoću Immunochip-a. Nakon navedenih analiza provedena je genomska asocijacijska studija. Ovo istraživanje pokazalo je da je šećerna bolest tipa 1 povezana s porastom oligomanoznih N-glikana i N-glikana s račvajućim N-acetilglukozaminom te padom monogalaktoziliranih N-glikana ukupnih plazmatskih proteina i IgG-a, kao i s porastom disijaliniziranih N-glikana IgG-a. Modeli temeljeni na N-glikanima proteina plazme su pokazali jako dobru diskriminacijsku moć između djece sa šećernom bolesti tipa 1 i njihovih zdravih srodnika (AUC > 0, 9). Identificiran je novi N-glikozilacijski lokus (komplement C3) povezan s razinama Man9 glikana plazmatskih proteina. S obzirom da se takav Man9 glikan nalazi na C3 domeni uključenoj u interakciju s patogenom, navedene promjene mogle bi potencijalno interferirati s aktivacijom sustava komplementa. Znanstveni doprinos ovog istraživanja je definicija N-glikozilacijskih promjena karakterističnih za ranu fazu šećerne bolesti tipa 1 i gena kojima su ove promjene regulirane. Navedeno je omogućilo razvoj prediktivnog modela šećerne bolesti tipa 1 koji bi mogao imati kliničku vrijednost te predložilo potencijalne mehanizme uključene u nastanak šećerne bolesti tipa 1.

Introduction: Macrophages frequently infiltrate injured glomerular and tubulointerstitial tissue, and it is possible that the degree and subtype of macrophage infiltration (M1 macrophages, which show proinflammatory features, and M2 macrophages, with their immunosuppressive features) varies depending on the type and severity of renal injury. Although renal involvement in patients with Henoch-Schönlein's purpura (HSP) is the main cause of morbidity and mortality and a significant prognostic determinant for the disease outcome, a reliable prognostic factor for severe forms of HSP nephritis (HSPN) is yet to be determined. Objectives: The aim of this research was to determine macrophage subclasses in renal biopsy specimens of HSPN patients and to analyze their quantity in regard with patients' clinical parameters and histologic features. Methods: We performed an immunohistochemical study on renal tissue samples of patients with HSPN, diagnosed by EULAR/PRINTO/PRES criteria and followed for at least 6 months. Patient clinical and laboratory data was retrieved from hospitals' medical records. Renal biopsy samples were marked with antibodies for CD68, iNOS and arginase. The number of immunoreactive cells was counted in each glomerulus by two independent experts. Results: Laboratory and histologic data for 25 patients with HSPN was evaluated in regard with macrophage infiltration of the renal tissue. The median glomerular M1 and M2 counts (q1, q3) were 2.3 (0.9, 12.2) and 7.6 (4.4, 13.9), respectively. M1 macrophages were found statistically significantly less frequent in the glomeruli in comparison with M2 macrophages (p < 0.001, b = -0, 289 ± 0.053). Collected laboratory data included inflammatory markers and markers of kidney function. There was no significant correlation between M1 and M2 macrophage count and laboratory parameters. Four pathohistological classifications were used: ISKDC, Haas classification, Oxford classification, and SQC classification. Classification stages/total classification scores and all histological variables were evaluated for possible correlation with macrophage count. Statistically significant negative correlation was found between segmental glomerulosclerosis (Oxford classification) and M2 macrophages (p = 0, 001, b = -1, 050 ± 0, 275). An indication of negative correlations was also noted between M2 macrophages and segmental sclerosis, and M2 macrophages and adhesions (SQC classification). Conclusion: Glomeruli in HSPN showed predominant M2 polarization of macrophages. M2 macrophage infiltration of glomeruli was highlighted as a possible negative predictor for segmental glomerulosclerosis. Grant/research support: Croatian Science Foundation project PURPURAPREDICTORS IP-2019-04- 8822 and University of Rijeka, Croatia grant No. Uni-ri-biomed-18-110.

Aspergilli section Nidulantes series Versicolores, producers of the mycotoxin sterigmatocystin (STC), dominated the fungi isolated from air and dust in flood-affected homes (Gunja) and control houses (Gornji Stupnik) in Croatia. The majority of isolates were able to produce STC and some isolates also produced its derivate 5- methoxysterigmatocystin (5-MET-STC). How can this affect human health? Here we present: a) Aspergilli series Versicolores species diversity in air and dust (calmodulin sequence-based methods) ; b) occurrence of STC and metabolites from the STC biosynthesis pathway in dust (LC- MS/MS) ; and c) immunomodulatory and genotoxic effects of STC and 5-MET-STC in lungs of male Wistar rats upon intratracheal instillation in concentrations found in dust. Most of the Versicolores isolates were from Gunja (91/125). Most isolates belonging to A. jensenii, A. creber, A. puulaauensis, A. tennesseensis, A. venenatus produced both STC and 5-MET-STC. A. amoenus, A. fructus, A. griseoaurantiacus, A. pepii and A. protuberus produced STC but not 5-MET-STC, while A. sydowii did not produce any of these two toxins. Among the 75 fungal compounds detected in dust, metabolites from the STC pathway including STC, 5-MET-STC, veriscolorin C, averufin and averantin were among the most abundant metabolites, which prevailed in repaired houses in Gunja. The highest concentrations of STC (0.59 µg/g) and 5-MET-STC (7.70 µg/g) in dust were detected in Gunja. In rat lungs, the immunomodulatory effects of STC (0.4 µg/mL) and 5- MET-STC (5 µg/mL) were insignificant. The levels of DNA damage were similar although STC was applied at a 10-fold lower dose. The results of combined treatment suggested possible antagonistic interactions. This work was fully supported by the Croatian Science Foundation under the project MycotoxA (IP-09-2014-5982).

Uvod. Makrofagi, kategorizirani kao M1 (kalprotektin+ podvrsta) ili M2 (CD163+ podvrsta) infiltriraju glomerule i tubulointersticij bubrega u bolesnika s Henoch-Schönlein-ovom purpurom (HSP- om). Broj tubulointersticijskih CD163+ makrofaga moćno predskazuje kronično bubrežno zatajivanje. Arginaza-1 jest biljeg svih M2 makrofaga, a inducibilna sintaza dušikovog oksida (iNOS) je biljeg svih klasično aktiviranih makrofaga M1. iNOS predstavlja aktivnost upalne bolesti, ukoliko je izražena na epitelnim stanicama crijeva. Međutim, uključenost iNOS u razvoju HSP-e je za sada neizvjesna. Cilj ovog rada je bio utvrditi raspodjelu CD68+, iNOS+ i arginaza-1+ stanica u bioptatu bubrega bolesnika s HSP-om te tkivni međuodnos CD68+ stanica i izvršnih imunoloških stanica CD3+ iCD56+ fenotipa. Ispitanici i metode. CD68, iNOS i arginaza-1 su obilježavani metodom imunohistologije (reakcija imunoperoksidaze uz vizualizaciju diaminobenzidinom), dok je dvostruko obilježavanje iNOS, arginaza-1, CD3 iliCD56 s CD68 biljegom učinjeno metodom dvostruke imunofluorescencije (uz vizualizacju primarnih mišjih ili zečjih protutijela sekundarnim protutijelima obilježenim fluorescentnim bojama Alexa fluor 488 i Alexa fluor 594) u biopsijama bubrega 22 bolesnika s nefritisom u sklopu HSP. Rezultati. Broj CD68+ stanica je podjednak u glomerulima [4, 6 (2, 6 ; 13, 7)] i tubulointersticiju [3, 3 (2 ; 6, 2)], [median (25. i 75. percentila)]. Također je podjednak broj arginaza-1+ i iNOS+ stanica u glomerulima, intersticiju i epitelnim stanicama tubula. U glomerulima i tubulima obilježile su se dvostruko pozitivne CD68+/iNOS+ stanice, međutim samo rijetke CD68+/arginaza-1+ stanice. MorfološkiCD68+ i iNOS+ stanice prepoznaju se kao razgranati makrofagi, ali i kao kuboidne tubularne epitelne stanice. Nakupine CD3+ limfocita utiskivale su se u intersticij, a znatno manje u glomerule, te nalazile u blizini makrofaga i tubularnih epitelnih stanica. CD56+ limfocitisu se rijetko obilježavali, uglavnom u glomerulima. Zaključak. Pored CD68+ makrofaga, tubularne epitelne stanice izražavaju CD68 i predstavljaju važan izvor iNOS- a, koje ograđuju brojniCD3+ limfociti. Funkcijski međuodnos iNOS+CD68+ stanica i limfocita tek treba istražiti, kao i njihovu povezanost s aktivnošću nefritisa. Financiranje istraživanja: projekt HRZZ br. IP- 2019-04-8822, projekt Sveučilišta u Rijeci br. Uni-ri-biomed- -18-110.