Immunosuppression in postweaning multisystemic wasting syndrome affected pigs

Veterinary Microbiology 98 (2004) 151–158

Immunosuppression in postweaning multisystemicwasting syndrome affected pigs

Joaquim Segalésa,∗, Mariano Domingoa, Francesca Chianinia, Natàlia Majóa,Javier Domınguezb, Laila Darwicha, Enric Mateua

a Departament de Sanitat i d’Anatomia Animals, Centre de Recerca en Sanitat Animal (CReSA),Universitat Autonoma de Barcelona, 08193 Barcelona, Spain

b INIA, SGIT, Ctra Coruña Km. 7, 28040 Madrid, Spain

Abstract

The present review concentrates on the clinical, pathological and immunological aspects of pigs suffering from PMWS whichstrongly suggest that PCV2 may be, in particular conditions, a cause of secondary immunodeficiency in pigs. From a clinicalpoint of view, the lack of antibiotic therapy response against the disease, the existence of a litter effect and the concurrence ofother disease syndromes and well-known secondary pathogens, such asPneumocystis carinii, Chlamydia spp. andAspergillusspp., may account as features of immunosuppression in PMWS. Furthermore, pathologic, immunohistologic and flow cytometricstudies also suggest that pigs with PMWS may be immunosuppressed. Lymphocyte depletion of follicular and interfollicularareas together with macrophage infiltration of lymphoid tissues is a unique lesion, which is the basic feature of PMWS affectedpigs. These findings are highly correlated with the decrease of circulating B- and T-cells and the diminution of these cell typesin lymphoid organs, and with the increase of macrophage/monocytes lineage cells both in peripheral blood and lymphoid tissuesin both naturally and experimentally PMWS affected pigs. The altered populations of cells participating in the immune systemresponse both in blood and tissues suggests, at least in those severely PMWS affected pigs, a transient inability of diseasedpigs to mount an effective immune response. From these points of view, strong suspicions on the immunosuppressive status ofPMWS affected pigs do exist; however, future studies are needed to characterise the exact role of PCV2 on the immune systemof pigs affected with PMWS.© 2003 Elsevier B.V. All rights reserved.

Keywords: Immunosuppression; Porcine circovirus type 2; Postweaning multisystemic wasting syndrome; Immunopathology; Flow cytometry

1. Introduction

Primary or secondary immunodeficiency increasesthe susceptibility of animals to infectious diseases

∗ Corresponding author. Tel.:+34-93-5811599;fax: +34-93-5813142.

E-mail address: [email protected] (J. Segales).

(Roth, 1999). Secondary immunodeficiency is a well-known consequence of some viral infections in ani-mals and humans. Viruses such as feline leukaemiavirus (FeLV), feline immunodeficiency virus (FIV)and human immunodeficiency virus (HIV) in-duce profound, long-lasting immunosuppression intheir respective hosts (English et al., 1993; Cotranet al., 1999). Other viruses as canine and feline

0378-1135/$ – see front matter © 2003 Elsevier B.V. All rights reserved.doi:10.1016/j.vetmic.2003.10.007

152 J. Segales et al. / Veterinary Microbiology 98 (2004) 151–158

parvoviruses may suppress immune responses tem-porarily (Trautwein and Hewicker-Trautwein, 1994).In pigs, several bacteria (Mycoplasma hyopneumo-niae, Actinobacillus pleuropneumoniae) and virusessuch as hog cholera virus, porcine reproductive andrespiratory syndrome (PRRSV), Aujeszky’s diseasevirus (ADV) are capable of suppressing immune func-tion sufficiently to make the animal more susceptibleto secondary infections. Furthermore, these and alsoother swine pathogens (porcine parvovirus (PPV),swine influenza virus, African swine fever virus andSalmonella spp.) are able to replicate in a variety ofimmune system cells and impair their function (Roth,1999).

Porcine circovirus type 2 (PCV2) is nowadays con-sidered the causal agent of postweaning multisystemicwasting syndrome (PMWS) (Bolin et al., 2001; Harmset al., 2001), an emerging disease affecting nursery andgrowing pigs worldwide (Allan and Ellis, 2000). Sev-eral lines of field and experimental evidence have sug-gested that severely PMWS affected pigs may developimmunosuppression. The present review concentrateson the clinical, pathological and immunological as-pects of pigs suffering from PMWS which stronglysuggest that PCV2 may be, in particular conditions, acause of secondary immunodeficiency in pigs.

2. PMWS clinical findings and concurrentinfections

PMWS most commonly affects pigs of 6–15 weeksof age, although the disease has been described in4–20-week-old pigs. Morbidity and lethality are vari-able depending on the farms and batches of animals,with rates varying 4–30 and 50–90%, respectively(Segalés et al., 2002a). The symptoms include wastingas major clinical sign but also pallor of the skin, res-piratory distress, diarrhoea and sometimes jaundice.In early descriptions of the disease, one of the mostsystematically recorded finding has been the lack ofefficiency of antimicrobial treatments despite the ex-istence of systemic and/or pulmonary bacterial infec-tions in these farms (Segalés et al., 1997; Hardinget al., 1998; Madec et al., 2000).

In addition, isolation of other infectious agents be-sides PCV2 from PMWS affected pigs, as PRRSV(Sorden et al., 1998; Rosell et al., 1999; Segalés

et al., 2002b), ADV (Rodrıguez-Arrioja et al., 1999;Rosell et al., 1999; Quintana et al., 2001), PPV (Elliset al., 2000), Haemophilus parasuis (Madec et al.,2000), Pasteurella multocida (Madec et al., 2000;Quintana et al., 2001) and Bordetella bronchisep-tica (Quintana et al., 2001), is a common finding inaffected farms. Furthermore,Pneumocystis carinii,Aspergillus spp. andChlamydia spp., considered op-portunistic pathogens commonly associated with im-munosuppression in animals and humans, have beenfound in lungs and/or intestine of PMWS affectedpigs (Clark, 1997; Carrasco et al., 2000; Segalés et al.,2003).

3. PMWS lesions in lymphoid tissues

Solid arguments to consider PMWS affected pigsas immunodepressed are derived from the histopatho-logical features of the disease (Clark, 1997; Rosellet al., 1999; Harms et al., 2001). Microscopic lesionsof lymphoid tissues in severely PMWS affected pigshave been extensively described, and include lympho-cyte depletion with loss of lymphoid follicles (B-celldependent areas mainly), and reduced cellularity inparafollicular T-cell dependent areas (Fig. 1A and B).Infiltration by large histocytic cells (epithelioid-likemacrophages) and multinucleate giant cells (MGCs)may be prominent at this stage (Fig. 2) (Clark, 1997;Rosell et al., 1999). In advanced stages, there ismacroscopic atrophy of lymphoid organs, mainlylymph nodes (Segalés et al., 2000a), which coin-cide microscopically with a generalised depletion oflymphoid cells, and prominent fibro-reticular stroma;medulla-like cords may appear severely cell depleted(Fig. 3). Areas previously occupied by lymphoid fol-licles may be empty of lymphoid cells, infiltrated withlarge histocytic cells, often showing many intracyto-plasmic inclusion bodies (Fig. 4).

A very high amount of PCV2 nucleic acid(Fig. 5) or antigen is usually present in the describedhistopathological lesions. Immune system cells suchas mononuclear-macrophage lineage and antigen pre-senting cells (APC) have shown to content PCV2in the cytoplasm and, sporadically, within the nuclei(McNeilly et al., 1999; Rosell et al., 1999); however,in situ hybridisation and immunohistochemical studieshave not been able to clearly demonstrate lymphocytes

J. Segales et al. / Veterinary Microbiology 98 (2004) 151–158 153

Fig. 1. (A) Mesenteric lymph node, non-PCV2 infected, healthypig. Normal lymphoid tissues showing the follicular and parafol-licular areas plenty of lymphocytes. H&E, magnification 50×. (B)Mesenteric lymph node, PMWS affected pig. Loss of lympho-cytes in follicular (B-cell dependent areas; note also the absenceof lymphoid follicles) and interfollicular zones (T-cell dependentareas). H&E, magnification 50×.

Fig. 2. Peyer’s patches, PMWS affected pig. Infiltration of largemononuclear (epithelioid-like macrophages) and MGCs in a fol-licular area. H&E, magnification 200×.

Fig. 3. Inguinal lymph node, PMWS affected pig. Severe lympho-cyte depletion with prominent fibro-reticular stroma and emptysubcapsular sinuses. H&E, magnification 20×.

Fig. 4. Tonsil, PMWS affected pig. Marked lymphocyte depletionin a follicular area, which is infiltrated by histocytic cells contain-ing high numbers of intracytoplasmic inclusion bodies of PCV2,magnification 200×.

infected by PCV2, neither in natural cases ofPMWS nor in experimentally PCV2 infected pigs(Rosell et al., 1999; Kennedy et al., 2000). Althoughwidespread infection of APC by PCV2 is a major fea-ture in PMWS, it is still unknown to what extent func-tion of these cells is affected by PCV2, and if the virusdirectly or indirectly mediates lymphoid depletion.

4. Immunopathology of lymphoid tissues ofPMWS affected pigs

The above-mentioned histopathological lesionshave been further characterised using immunohisto-


Fig. 5. Mesenteric lymph node, PMWS affected pig. High amountof PCV2 nucleic acid in cytoplasm and/or nuclei of histocyticcells located in medullary sinuses. In situ hybridisation and fastgreen counterstain, magnification 100×.

Fig. 6. (A) Inguinal lymph node, non-PCV2 infected, healthypig. Normal distribution of CD3 positive cells (T lymphocytes)in interfollicular areas. Immunohistochemistry for CD3, haema-toxylin counterstain, magnification 10×. (B) Inguinal lymph node,PMWS affected pig. Marked reduction of cells expressing theCD3 molecule (T lymphocytes) in the lymph node parenchyma.Immunohistochemistry for CD3, haematoxylin counterstain, mag-nification 10×.

Fig. 7. (A) Inguinal lymph node, non-PCV2 infected, healthypig. APCs are mainly located in lymphoid follicles and, in lessernumbers, in the interfollicular areas. Immunohistochemistry forSLA-II DQ (using antibody BL2H5), haematoxylin counterstain,magnification 100×. (B) Inguinal lymph node, PMWS affectedpig. Slight loss and redistribution of APCs in a diffuse pattern.Immunohistochemistry for SLA-II DQ (using antibody BL2H5),haematoxylin counterstain, magnification 100×.

chemical methods (Shibahara et al., 2000; Sarli et al.,2001; Chianini et al., 2003). These changes consistof moderate to marked reduction or loss of B-cells,diminution of T lymphocytes (Fig. 6A and B), in-crease of subcapsular and peritrabecular macrophages,and partial loss and redistribution of APC throughoutlymphoid tissues (Fig. 7A and B) (Chianini et al.,2003). The severity of these changes were stronglycorrelated with the severity of PMWS histological le-sions and the higher amount of PCV2 antigen and/ornucleic acid. Depletion of T cells has been associatedto a decrease of CD4 positive cells and, to a minorextent, of CD8 positive cells (Sarli et al., 2001).

The mechanism by which lymphoid depletion oc-curs in PMWS has not been elucidated yet. It has been


suggested that lymphocyte depletion may occur by anindirect pathway in which apoptosis, cytokine imbal-ance, and alteration of migration pathways may beimplicated (Shibahara et al., 2000). This hypothesiscomes from the fact that a low number of lymphocytesare infected by PCV2 when measured by in situ hy-bridisation or immunohistochemical methods, while ahigh number of apoptotic B lymphocytes are observedin lymphoid tissues of severely PMWS affected pigs(Shibahara et al., 2000).

5. Peripheral blood mononuclear cell (PBMC)subsets in PMWS

Changes in PBMC subsets in PMWS have beendocumented. In one study, naturally PMWS affectedpigs had a lower mean of lymphocyte percentagesthan clinically healthy animals, although this differ-ence was not statistically significant (Segalés et al.,2000b). However, when the total lymphocyte countsfrom PMWS affected pigs without gastric ulcerationof pars oesophagea of the same study are comparedwith those from healthy pigs (data not published), asignificantly higher standard deviation is observed indiseased pigs. Furthermore, taking the blood value of3600 lymphocytes/ml as the minimal normal lympho-cyte counts for growing pigs (Friendship and Henry,1992), 16 out of 29 pigs of these PMWS affected pigshad lymphopenia, while none of the healthy pigs hadlower lymphocyte total counts than the minimal nor-mal counts. Therefore, lymphopenia is a feature ofsome PMWS affected pigs.

On the other hand, the same study showed an in-creased mean percentage and total count of monocytesin pigs suffering from PMWS, suggesting an increaseor proliferation of monocyte/macrophage lineage cellsinduced by PCV2 infection. This last result correlateswith the increase of macrophages infiltrating lymphoidtissues of diseased pigs (Rosell et al., 1999; Chianiniet al., 2003).

Two studies have focused on the analysis of PBMCof naturally PMWS affected pigs using flow cytome-try and several monoclonal antibodies (Segalés et al.,2001; Darwich et al., 2002). In one of these stud-ies, conventional pigs of a high sanitary status, freeof most viral and bacterial infections, were comparedwith acutely PMWS affected pigs also free of other

major pathogens (PRRSV and ADV) of pigs (Segaléset al., 2001). A significant reduction in circulatingCD3 and CD4 positive cells and a marked increase incirculating cells expressing SLA-II antigens was ob-served. Also, more than a half of the diseased pigshad also a strong reduction of IgM positive circulatingcells (B lymphocytes). Noteworthy, immature granu-locytes were detected in PMWS affected pigs, whichis consistent with the frequently observed bronchop-neumonia in diseased pigs.

A study of a higher number of natural cases ofPMWS submitted for necropsy (Darwich et al., 2002)has extended the previous data on the decrease incirculating IgM positive cells (B lymphocytes). Thisreduction was clearly correlated with histopathologi-cal findings of lymphoid depletion of B-cell areas inlymphoid tissues. A reduction in CD4 positive cellswas also detected in PMWS and wasted, non-PCV2infected pigs, when compared with normal pigs. Bycontrast, a reduction of CD8 and CD4/CD8 positivecells was observed only in the group of pigs affectedby PMWS; therefore, a specific decrease of circulat-ing CD8 positive cells induced by PCV2 infection wassuggested.

These results obtained in naturally PMWS affectedpigs have been confirmed when studying experimen-tally PCV2 infected pigs developing wasting disease(Nielsen et al., 2001). Three out of five pigs infectedwith the virus developed a severe PMWS; these an-imals had a marked reduction in CD4 positive cellsand B lymphocytes when compared with control pigsand these animals infected with PCV2 that not de-veloped clinical disease. Also, CD8 and CD4/CD8double positive cells were also reduced in number ininfected pigs.

6. Discussion

From a clinical point of view, immunodeficiencyis usually associated to (1) illness from organisms ofnormally low pathogenicity or from an attenuated livevaccine, (2) recurrent illnesses that are usually difficultto control, (3) failure to respond adequately to vac-cination, (4) unexplained neonatal illness and deathaffecting more than one animal in a litter, and (5) a va-riety of disease syndromes occurring concurrently ina herd (Roth, 1999). Some of these findings have been


extensively described in PMWS. The lack of antibiotictherapy response (Segalés et al., 1997; Hardinget al., 1998), the existence of a litter effect (Madecet al., 2000) and the concurrence of other diseasesyndromes (Rodrıguez-Arrioja et al., 1999; Madecet al., 2000; Quintana et al., 2001; Segalés et al.,2002b) and well-known secondary pathogens (Clark,1997; Carrasco et al., 2000; Segalés et al., 2003)may account as features of immunosuppression inPMWS.

On the other hand, pathologic, immunohistologicand flow cytometric studies also suggest that pigs withPMWS may be immunosuppressed. Lymphocyte de-pletion of follicular and interfollicular areas togetherwith macrophage infiltration of lymphoid tissues is aunique lesion, which is the basic feature of PMWSaffected pigs (Clark, 1997; Rosell et al., 1999). Thesefindings are highly correlated with the decrease ofcirculating B- and T-cells and the diminution of thesecell types in lymphoid organs, and with the increase ofmacrophage/monocytes lineage cells both in periph-eral blood and lymphoid tissues (Nielsen et al., 2001;Segalés et al., 2001; Darwich et al., 2002; Chianiniet al., 2003). Surprisingly, lymphopenia was not afeature in PMWS when a group of 50 affected pigswas considered (Segalés et al., 2000b). However, aproportion of these PMWS affected pigs had an ap-parent transient lymphopenia, which would correlatewith the published pathological and immunologicalstudies. Finally, APC, such as dendritic follicularand interdigitating cells, has also been demonstratedto content PCV2 nucleic acid and changes in theirtissular distribution have been described (Chianiniet al., 2003). Therefore, the altered populations ofcells participating in the immune system responseboth in blood and tissues suggests, at least in thoseseverely PMWS affected pigs, a transient inabil-ity of diseased pigs to mount an effective immuneresponse.

In general, the potential mechanisms for virus-induced immunosuppression include changes in im-mune function as a direct consequence of virusreplication in cells that participate in the immuneresponse, changes in immune function as an indirectconsequence of the normal host immune response tothe infecting virus, and indirect effects of virus repli-cation (Griffin, 1997). More specifically, viruses areknown to cause immunosuppression by interfering

with antigen presentation, by the induction of apop-tosis of immune system cells, by acting as cytokinesor cytokines inhibitors/enhancers or by inhibiting thecomplement (Drew, 2000). From these points of view,although strong suspicions on the immunosuppressivestatus of PMWS affected pigs have been presentedin this review, future studies on the in vitro and invivo replication in cells on the immune system andits function, the effects of the host antiviral immuneresponse and the effects of viral proteins on immunefunction are needed to assess the exact role of PCV2on the immune system of pigs affected with PMWS.

Acknowledgements

We would like to thank all researchers and techni-cians from the Pathology Department at the Veteri-nary School of Barcelona for their help and assistanceon the study of PMWS and PCV2 infection in thelast 4 years: M. Calsamiglia, P. Losada, B. Pérez,M. Pérez, J. Quintana, A. Resendes, R. Rivas, G.M.Rodrıguez-Arrioja, C. Rosell, A. Rovira, M. Sibilaand S. Usero. We also thank the concession of theprojects QLRT-PL-199900307 from the Fifth Frame-work Programme 1998–2002 of the European Com-mission, and 2-FEDER-1997-1341 from the I+ DNational Plan (Spain).

References

Allan, G.M., Ellis, J.A., 2000. Porcine circoviruses: a review. J.Vet. Diagn. Invest. 12, 3–14.

Bolin, S.R., Stoffregen, W.C., Nayar, G.P., Hamel, A.L.,2001. Postweaning multisystemic wasting syndrome inducedafter experimental inoculation of cesarean-derived, colostrum-deprived piglets with type 2 porcine circovirus. J. Vet. Diagn.Invest. 13, 185–194.

Carrasco, L., Segalés, J., Bautista, M.J., Gómez-Villamandos,J.C., Rosell, C., Ruiz-Villamor, E., Sierra, M.A., 2000.Intestinal chlamydial infection concurrent with postweaningmultisystemic wasting syndrome in pigs. Vet. Rec. 146, 21–23.

Chianini, F., Majo, N., Segales, J., Dominguez, J., Domingo,M., 2003. Immunohistochemical characterisation of PCU2associate lesions in lymphoid and non-lymphoid tissues of pigswith natural post weaning multisystemic wasting syndrome(PMWS). Vet. Immunol. Immunopathol. 94, 63–75.

Clark, E.G., 1997. Post-weaning multisystemic wasting syndrome.In: Proceedings of the 28th American Association of SwinePractitioners, pp. 499–501.


Cotran, R.S., Kumar, V., Collins, T., 1999. Diseases of immunity.In: Cotran, R.S., Kumar, V., Collins, T. (Eds.), PathologicBasis of Disease. W.B. Saunders Company, Philadelphia, PA,pp. 188–259.

Darwich, L., Segalés, J., Domingo, M., Mateu, E., 2002. Changesin the CD4+, CD8+, CD4/CD8 double positive cells andIgM+ cell subset in peripheral blood mononuclear cells frompostweaning multisystemic wasting syndrome affected pigs andage matched uninfected wasted and healthy pigs. Clin. Diagn.Lab. Immunol. 9, 236–242.

Drew, T.W., 2000. A review of evidence for immunosuppressiondue to porcine reproductive and respiratory syndrome virus.Vet. Res. 31, 27–39.

Ellis, J.A., Bratanich, A., Clark, E.G., Allan, G., Meehan,B., Haines, D.M., Harding, J., West, K.H., Krakowka, S.,Konoby, C., Hassard, L., Martin, K., McNeilly, F., 2000.Coinfection by porcine circoviruses and porcine parvovirusin pigs with naturally acquired postweaning multisystemicwasting syndrome. J. Vet. Diagn. Invest. 12, 21–27.

English, R.V., Johnson, C.M., Gebhard, D.H., Tompkins, M.B.,1993. In vivo lymphocyte tropism of feline immunodeficiencyvirus. J. Virol. 67, 5175–5186.

Friendship, R.B., Henry, S.C., 1992. Cardiovascular system,hematology and clinical chemistry. In: Leman, A.D., Straw,B.E., D’Allaire, S., Mengeling, W.L., Taylor, D.J. (Eds.),Diseases of Swine, 7th ed. Iowa State University Press, Iowa,pp. 1–20.

Griffin, D.E., 1997. Virus-induced immune suppression. In:Ahmed, R., Gonzalez-Scarano, F., Griffin, D.E., Holmes, K.V.,Murphy, F.A., Robinson, H.L. (Eds.), Viral Pathogenesis.Lippincot-Raven Publishers, pp. 207–234.

Harding, J.C.S., Clark, E.G., Strokappe, J.H., Willson, P.I., Ellis,J.A., 1998. Postweaning multisystemic wasting syndrome:epidemiology and clinical presentation. Swine Health Prod. 6,249–254.

Harms, P.A., Sorden, S.D., Halbur, P.G., Bolin, S.R., Lager, K.M.,Morozov, I., Paul, P.S., 2001. Experimental reproduction ofsevere disease in CD/CD pigs concurrently infected with type2 porcine circovirus and porcine reproductive and respiratorysyndrome virus. Vet. Pathol. 38, 528–539.

Kennedy, S., Moffett, D., McNeilly, F., Meehan, B., Ellis, J.,Krakowka, S., Allan, G.M., 2000. Reproduction of lesions ofpostweaning multisystemic wasting syndrome by infection ofconventional pigs with porcine circovirus type 2 alone or incombination with porcine parvovirus. J. Comp. Pathol. 122,9–24.

Madec, F., Eveno, E., Morvan, P., Hamon, L., Blanchard, P.,Cariolet, R., Amenna, N., Morvan, H., Truong, C., Mahé,D., Albina, E., Jestin, A., 2000. Post-weaning multisystemicwasting syndrome (PMWS) in pigs in France: clinicalobservations from follow-up studies on affected farms. Livest.Prod. Sci. 63, 223–233.

McNeilly, F., Kennedy, S., Moffett, D., Meehan, B.M., Foster,J.C., Clarke, E.G., Ellis, J.A., Haines, D.M., Adair, B.M.,Allan, G.M., 1999. A comparison of in situ hybridizationand immunohistochemistry for the detection of a newporcine circovirus in formalin-fixed tissues from pigs with

post-weaning multisystemic wasting syndrome (PMWS). J.Virol. Meth. 80, 123–128.

Nielsen, J., Vincent, I., Ladekjaer-Mikkelsen, A.S., Allan, G.,McCullough, K., Botner, A., 2001. Experimental infection of3-week-old piglets with PCV2 altered the level of variousperipheral blood leukocyte populations. In: Proceedings of thessDNA Viruses of Plants, Birds, Pigs and Primates: PorcinePost-weaning Multisystemic Wasting Syndrome. EuropeanSociety of Veterinary Virology, p. 96.

Quintana, J., Segalés, J., Rosell, C., Calsamiglia, M., Rodrıguez-Arrioja, G.M., Chianini, F., Folch, J.M., Maldonado, J.,Canal, M., Plana-Duran, J., Domingo, M., 2001. Clinicaland pathological observations on pigs with postweaningmultisystemic wasting syndrome. Vet. Rec. 149, 357–361.

Rodrıguez-Arrioja, G.M., Segalés, J., Rosell, C., Quintana, J.,Ayllón, S., Camprodón, A., Domingo, M., 1999. Aujeszky’sdisease virus infection concurrent with postweaning multi-systemic wasting syndrome in pigs. Vet. Rec. 144, 152–153.

Rosell, C., Segalés, J., Plana-Durán, J., Balasch, M., Rodrıguez-Arrioja, G.M., Kennedy, S., Allan, G.M., McNeilly, F., Latimer,K.S., Domingo, M., 1999. Pathological, immunohistochemical,and in-situ hybridization studies of natural cases ofpostweaning multisystemic wasting syndrome (PMWS) in pigs.J. Comp. Pathol. 120, 59–78.

Roth, J.A., 1999. The immune system. In: Straw, B.E., D’Allaire,S., Mengeling, W.L., Taylor, D.J. (Eds.), Diseases of Swine,8th ed. Iowa State University Press, Iowa, pp. 799–820.

Sarli, G., Mandrioli, L., Laurenti, M., Sidoli, L., Cerati, C., Rolla,G., Marcato, P.S., 2001. Immunohistochemical characterizationof the lymph node reaction in pig postweaning multisystemicwasting syndrome (PMWS). Vet. Immunol. Immunopathol. 83,53–67.

Segalés, J., Sitjar, M., Domingo, M., Dee, S., Del Pozo, M.,Noval, R., Sacristán, C., De las Heras, A., Ferro, A., Latimer,K.S., 1997. First report of post-weaning multisystemic wastingsyndrome in pigs in Spain. Vet. Rec. 141, 600–601.

Segalés, J., Rosell, C., Rodrıguez-Arrioja, G., Domingo, M., 2000a.Patologıa de la circovirosis porcina. Porci 56, 41–54.

Segalés, J., Pastor, J., Cuenca, R., Domingo, M., 2000b.Haematological parameters in postweaning multisystemicwasting syndrome-affected pigs. Vet. Rec. 146, 675–676.

Segalés, J., Alonso, F., Rosell, C., Pastor, J., Chianini, F., Campos,E., López-Fuertes, L., Quintana, J., Rodrıguez-Arrioja, G.,Calsamiglia, M., Pujols, J., Domınguez, J., Domingo, M., 2001.Changes in peripheral blood leukocyte populations in pigs withnatural postweaning multisystemic wasting syndrome (PMWS).Vet. Immunol. Immunopathol. 81, 37–44.

Segalés, J., Madec, F., Domingo, M., 2002a. Postweaningmultisystemic wasting syndrome and porcine circovirus type2: the European perspective. In: Zimmerman, J.J., Yoon, K.J.,Morilla, A. (Eds.), Trends in Emerging Viral Diseases of Swine.Iowa State University Press, Iowa.

Segalés, J., Calsamiglia, M., Rosell, C., Soler, M., Maldonado,J., Martın, M., Domingo, M., 2002b. Porcine reproductive andrespiratory syndrome virus (PRRSV) infection status in pigsnaturally affected with post-weaning multisystemic wastingsyndrome (PMWS) in Spain. Vet. Microbiol. 85, 23–30.


Segalés, J., Collell, M., Jensen, H.E., Blanco, J.L., Domingo, M.,2003. Pulmonary Aspergillosis in a postweaning multisystemicwasting syndrome (PMWS) affected pigs. Pig J. 52, 41–47.

Shibahara, T., Sato, K., Ishikawa, Y., Kadota, K., 2000. Porcinecircovirus induces B lymphocyte depletion in pigs with wastingdisease syndrome. J. Vet. Med. Sci. 62, 1125–1131.

Sorden, S.D., Harms, P.A., Sirinarumitr, T., Morozov, I., Halbur,P.G., Yoon, K.J., Paul, P.S., 1998. Porcine circovirus and

PRRSV co-infection in pigs with chronic bronchointerstitialpneumonia and lymphoid depletion: an emerging syndromein midwestern swine. In: Proceedings of the Annual Meetingof the American Association of Veterinary LaboratoryDiagnosticians, Minneapolis, MN.

Trautwein, G., Hewicker-Trautwein, M., 1994. Immunopatho-genesis of virus diseases of cats and dogs. Tierarztl Prax. 22,63–72.

Documents

Immunosuppression in postweaning multisystemic wasting syndrome affected pigs