Anette Solveig Debertin

Nasal‐associated lymphoid tissue (NALT): frequency and localization in young children

In mucosal immunology nasal‐associated lymphoid tissue (NALT) is taken as a constitutive structure of the nasal immune system and as a target tissue in strategies of local defence and an induction site for vaccination. These concepts are based on findings in rodents, but it has not been investigated systematically whether NALT also is present in humans and if so in which amount and localization. In a postmortem study the presence of NALT in humans is documented as a morphologically distinct structure additional to the lymphoid structures of the Waldeyers ring. Human nasal tissue blocks of 150 children who had died in the first two years of life either of sudden infant death (n = 109) without signs of respiratory tract infections or of different traumatic (n = 22) and natural causes of death (n = 19) were obtained using a specific autopsy‐technique and were investigated systematically using histology. Clearly in contrast to rodents human NALT was found disseminated in the nasal mucosa with typical morphological features in 38% of all children, mainly in the middle concha, with similar morphology and frequency in the examined groups. No correlation was found between the presence of NALT and the cause of death and especially the grade of inflammation in general. Therefore, NALT might be the morphological basis for inhalative vaccination strategies in young children and play a role in mucosal host defence.

Age‐dependent histoarchitectural changes in human lymph nodes: an underestimated process with clinical relevance?

Experimental evidence indicates that lymph nodes in humans undergo alterations during ageing. This is clinically important because of the crucial role of these organs in the immune system and their lymph reabsorption and drainage function. Although some age‐related changes in lymph node histoarchitecture have been described, they are seldom taken into account in traditional depictions of lymph nodes. Recently introduced clinical procedures, such as intranodal vaccination or lymph node transplantation, have demonstrated the need for an accurate knowledge of these degenerative processes. In this study, superficial inguinal lymph nodes were obtained from 41 deceased patients between 17 and 98 years old. To minimize immunological influences, such as chronic diseases, specimens were only obtained from forensic pathology autopsies. An immunohistochemical analysis was carried out, on the basis of which lymph node degeneration was scored according to the numbers of lymphocytes and high endothelial venules, and degree of fibrosis and lipomatosis. We observed an age‐dependent tendency towards the replacement of areas populated with diverse immune cells by connective tissue. Paradoxically, these changes were also detected in some of the nodes from younger age groups. In conclusion, lymph nodes can display degenerative changes that are mainly age‐related and often diverge from the common description found in textbooks. These alterations should be taken into account when dealing with lymph nodes diagnostically and therapeutically in clinical practice.

Coincidence of different structures of mucosa-associated lymphoid tissue (MALT) in the respiratory tract of children: no indications for enhanced mucosal immunostimulation in sudden infant death syndrome (SIDS)

Mucosa‐associated lymphoid tissue (MALT) is the principal inductive site for mucosal immune responses that are capable of T and B cell responses and antigen‐specific responses. In previous independent studies different structures of MALT, e.g. bronchus‐, larynx‐ and nose‐associated lymphoid tissue (BALT, LALT, NALT) have been described separately in various frequencies in the human respiratory tract over life spans. Because upper respiratory tract infections are common in infants, dysregulations of mucosal immune responses might be seriously involved in the aetiology of sudden infant death syndrome (SIDS). In the present study the coincidental occurrence of the three different MALT structures in the respiratory tract within the same patients were studied, and cases of SIDS and children who had died from different traumatic and natural causes of death (non‐SIDS) were compared. First, the frequency of BALT and LALT in 46 children (35 SIDS, 11 non‐SIDS) with or without NALT were examined. A tendency was found of a coincidence of respiratory MALT structures. In 50 additional cases of infant death (30 SIDS, 20 non‐SIDS) from the multi‐centric German Study on Sudden Infant Death Syndrome (GeSID) where death had occurred in the first year of life, the coincidence was evaluated. A coincidental occurrence of BALT, LALT and NALT or BALT and LALT (each about 30%) was found in both groups, whereby the coincidence in SIDS and the control patients did not differ. Interestingly, the children with coincidental MALT were strikingly older, supporting the hypothesis of respiratory MALT formation via environmental stimulation over time.

Serum procalcitonin levels in the postmortem diagnosis of sepsis

Procalcitonin is regarded as a valuable marker for sepsis in living persons and even in post-mortem investigations. At the Institute of Legal Medicine, 25 autopsy cases with suspected bacterial infectious diseases or sepsis were examined using the semi-quantitative PCT-Q(®)-test (B.R.A.H.M.S., Germany) in 2010 and 2011. As controls, 75 cadavers were used for which there was no suspicion of a bacterial infectious disease or sepsis. Femoral blood was cultured from the cases and from controls, and samples from the brain, heart, lungs, liver, spleen and kidneys were examined histologically for findings seen in sepsis. Twelve cases in the sepsis/infectious disease group (48%) were classifiable as sepsis following synopsis of PCT levels, autopsy results, and histopathological and microbiological findings. This study shows that the semi-quantitative PCT-Q(®)-test is a useful supplementary marker in routine autopsy investigations, capable of classifying death as due to sepsis.

Tissue distribution of components of the insulin-like growth factor system in sudden infant death and controls

Growth factors may be involved in sudden infant death (SID). Among these factors, the insulin-like growth factor (IGF) family is important in human fetal and perinatal organ growth and development. In order to detect probable differences in the occurrence and distribution of components of the IGF system, tissue samples from liver, lung, skin, parotid and thyroid gland, gut and cerebellum from SID children (n=9) and controls (n=6) aged between 14 and 258 days of life (mean 105 days) were stained immunohistochemically using antibodies against IGF-I, IGF-II and their specific IGF-I-receptor (IGF-IR). In contrast to controls in hepatocytes of SID children a reduction or an absence of immunoreactivity for IGF-I and IGF-IR and a weaker staining for IGF-II was detected. IGF-II in smooth muscle layers in the gut and IGF-I in epithelial cells in intestinal specimens also showed a reduced immunoreactivity in SID children and those who died traumatic deaths. In the other organs examined no significant differences in the distribution of the insulin-like growth factor system between the groups could be detected, indicating that in SID children no fundamental differences or alterations in the physiology of the IGF system occur. Because of the decreased immunostaining of IGFs in the liver and intestine of SID cases, a local dysregulation may be discussed.