**1. Introduction**

McGraw-Hill Concise Dictionary of Modern Medicine [1] defines pulmonary-renal syndrome (PRS) as an idiopathic condition characterized by pulmonary hemorrhage, rapid progressive glomerulonephritis, and positive autoantibodies. Pulmonary-renal syndrome may be also defined as a heterogeneous group of multisystem diseases – e.g. Goodpasture syndrome, Wegener's granulomatosis, collagen vascular disease – in particular systemic lupus erythematosus, polyarteritis nodosa, Henoch-Schönlein purpura, and various other conditions, which all have prominent pulmonary and renal components. According to Sanders [2] the strict definition of pulmonary-renal syndrome is the combined clinical picture of rapid progressive glomerulonephritis and pulmonary capillaritis requiring histological confirmation.

If we translate the definition into pathological nomenclature, pulmonary-renal syndrome is defined as combination of diffuse alveolar hemorrhage (DAH) and immune crescent glomerulonephritis. The essential substrate of all these changes is vasculitis, which is according to contemporary nomenclature based mostly on morphological and histopathological criteria. These criteria for the most common forms of vasculitides were introduced in 1994 by Jennette et al. at the Chapel Hill Consensus Conference organized by the American College of Rheumatology [3]. The inflammation of small vessels (microangiopathic vasculitis) restricts blood flow to various organs and damages them. If correct diagnosis and appropriate treatment are delayed the condition can be fatal. Prognosis is good when treatment begins before onset of respiratory and renal failure. Because of the similarity in clinical picture, differential diagnosis of these diseases at the bedside can be challenging.

The pathophysiology of the vasculitides is based on immunologic mechanisms. These appear to play an active role in mediating the inflammatory response, but their exact mechanisms still

© 2013 Lukán; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

remain poorly understood. Although the primary events that initiate this process remain largely unknown, recent investigations have brought us closer to understanding some of the critical pathways involved in disease and provided a rationale for the study of novel therapeutic agents [4].

Jennette et al. [13] described pathologic features of different necrotizing vasculitis types indicating various pathogenic mechanisms causing the injury. In anti-GBM disease or immune complex disease the pathogenic complexes between antibodies and antigens are located exclusively or predominantly in vessel walls. In patients with ANCA vasculitis, these autoantibodies are in the interstitial fluid and also in the blood. ANCA activate neutrophils and monocytes in blood vessels, as well as in interstitial tissue. Activation in the vessels causes necrotizing vasculitis and activation in the tissues necrotizing tissue inflammation. Clinical

Immunological Mechanisms and Clinical Aspects in Pulmonary-Renal Syndrome: A Review

http://dx.doi.org/10.5772/55181

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association of dominating organs in pulmonary-renal syndrome is shown in table 1.

Organ **MPA GPA (WG) CSS GPS** Kidney 90 80 45 75 Lung 50 90 70 60

Interstitial inflammation is accompanied by capillary trombosis, disintegration of blood vessel wall, loss of integrity of tissue structures, epithelial cell hyperplasia, accumulation of red cells (and later hemosiderin), depositions of proteins (immunoglobulins, immune-complex proteins), interstitial fibrosis and atrophy. The actual picture is dependent on different organ

Presence of specific granulomatous inflammation is typical for granulomatosis with polyangiitis (GPA, formerly Wegener´s granulomatosis) described and defined by Wegener in 1939 [14] and Former in 1950 [15] respectively. Morphological detected recruitment of inflammatory cells, as well as immune competent cells (T-cells, B, cells, macrophages) and sometimes also giant-cells are confirmed by immunostaining of autoantibodies, detection of

Pulmonary-renal syndrome has a wide spectrum of organ histopathological changes. Severe renal vascular damage can be accomapnied by absent or mild pulmonary changes. On the other hand severe pulmonary injury can be followed by mild renal destruction or normal renal

Renal pathology is expressed by various forms of glomerulonephritis (anti-GBM, immunocom‐ plex, necrotizing pauci-immune). In rare cases sequential development supposed to be of pathogenic importance: injury caused by ANCA may uncover the Goodpasture antigen. The

Immunohistochemical classification of renal capillary vasculitides [17] based on renal biopsies

concept that only one antigen may trigger another one requires further support [16].

**Table 1.** Approximate frequency of organ system involvement (%)

cytokine release and oxygen-free radical formation.

histology.

**3.1. Renal pathology**

is characterized by the presence of:

**1.** anti GBM antibodies – type I crescentic GN **2.** immune complexes – type II crescentic GN

structure of lungs and kidneys, as well as on primary stimulus.
