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Year : 2017  |  Volume : 34  |  Issue : 1  |  Page : 85-87  

A severe Mycoplasma pneumoniae pneumonia inducing an acute antibody-mediated pulmonary graft rejection

1 Department of Pulmonary Diseases, Lyon University Hospital System, Louis Pradel Hospital, F-69003, Lyon, France
2 Department of Infectious Diseases, Lyon University Hospital System, Croix Rousse Hospital, F-69004; International Center for Infectiology Research, Inserm U1111, Lyon 1 University, F-69007, Lyon, France
3 Department of Pulmonary Diseases, Lyon University Hospital System, Louis Pradel Hospital, F-69003; Viral Infections and Comparative Pathology, INRA UMR 754, Lyon 1 University, F-69007, Lyon, France

Date of Web Publication30-Dec-2016

Correspondence Address:
Jean-Francois Mornex
Department of Pulmonary, Louis Pradel Hospital, Hospices Civils de Lyon, F-69500, Bron
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-2113.197104

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A 40-year-old cystic fibrosis woman with a history of double-lung transplantation 2 years previously was admitted for a progressive respiratory distress. Physical examination revealed fever (39°C) and diffuse bilateral lung crackles. Laboratory findings included severe hypoxemia and inflammatory syndrome. Bronchoalveolar lavage and serological test were positive for mycoplasma pneumonia. As the patient did not improve after 3 days of antibiotics and donor-specific HLA antibodies had been detected, an acute antibody-mediated graft rejection was treated with high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and rituximab. The patient rapidly improved. Unfortunately, 6 months after this episode, she developed a bronchiolitis obliterans syndrome with a dependence to noninvasive ventilator leading to the indication of retransplantation. This case illustrates the possible relationship between infection and humoral rejection. These two diagnoses should be promptly investigated and systematically treated in lung transplant recipients.

Keywords: Antibody mediated, graft rejection, Mycoplasma pneumoniae, pneumonia

How to cite this article:
Demir S, Saison J, Sénéchal A, Mornex JF. A severe Mycoplasma pneumoniae pneumonia inducing an acute antibody-mediated pulmonary graft rejection. Lung India 2017;34:85-7

How to cite this URL:
Demir S, Saison J, Sénéchal A, Mornex JF. A severe Mycoplasma pneumoniae pneumonia inducing an acute antibody-mediated pulmonary graft rejection. Lung India [serial online] 2017 [cited 2019 Nov 13];34:85-7. Available from: http://www.lungindia.com/text.asp?2017/34/1/85/197104

   Introduction Top

The role of infections in the graft rejection remains unclear. The lung transplant, in contrast with other transplanted organs, can often be infected, notably by respiratory infectious agents. The present case illustrate the potential role of such respiratory infection in organ rejection.

   Case Report Top

A 40-year-old Caucasian woman with a lifelong history of cystic fibrosis was admitted for a progressive respiratory distress upon return by plane from Turkey. The patient had noted over the previous 4 days a progressive onset of fever, dry cough, and dyspnea. She had undergone double-lung transplantation 2 years previously. Sequential bilateral lung transplantation had been performed after the placement of an extracorporeal membrane oxygenation and included immunosuppressive induction with basiliximab. Two months previously, the patient was in good general health including normal pulmonary function test. Because of persistent abdominal pain and diarrhea, trimethoprim-sulfamethoxazole prophylaxis had been stopped and immunosuppressive therapy by mycophenolate mofetil (2 g every day) and tacrolimus (3 mg every day) switched to azathioprine (100 mg every day) and cyclosporin (175 mg bid), associated with corticosteroids at 5 mg every day. Subsequently, digestive symptoms resolved following this medication change.

Physical examination revealed fever (39°C), diffuse bilateral lung crackles, and no extrapulmonary signs. Arterial oxygen pressure was 51 mmHg. There was an inflammatory biological syndrome with elevated leukocyte count (17 G/L, normal <10 G/L), C-reactive protein (266 mg/L, normal <5 mg/L), and no kidney insufficiency. Hepatic test revealed mild cytolysis with elevated serum glutamo oxaloacetate transferase (83 U/L, normal <34 U/L), normal serum glutamate pyruvate transaminase, and no cholestasis. Cyclosporin residual level was in therapeutic range (133 µg/L). There was no cardiac dysfunction on echocardiography. Chest radiography and computed tomography revealed bilateral pneumonia [Figure 1]a and ruled out pulmonary embolism. After blood culture and bronchoscopy with bronchoalveolar lavage (BAL), empirical antibiotics were started with trimethoprim-sulfamethoxazole, piperacillin-tazobactam, amikacin, and erythromycin. As the acute respiratory failure was worsening, the patient was transferred to the intensive care unit the same day. However, mechanical ventilation was not necessary and high-flow (fraction of inspired oxygen between 50 and 60%) oxygenation was performed with inspired air humidification system (Optiflow @). Mycoplasma pneumonia was detected by polymerase chain reaction (PCR) in BAL samples. No other infectious agent was detected, in particular no Pneumocystis jirovecii. After 3 days of antibiotics, as the patient did not improve, i.e., persistent severe hypoxemia, fever, biological inflammatory syndrome, and radiographic diffuse lung opacities; the diagnosis of acute graft antibody-mediated rejection (AMR) was suggested based on the detection of specific HLA antibodies (DSA) anti-DQ4 and anti-DQA1*03 detection (Luminex Technic, kit LSA Class II Immunocor). Because of the severity of the respiratory insufficiency, transbronchial lung biopsies were not performed. Treatment was started associating (i) three boluses of prednisolone (500 mg every day) followed by 1 mg/kg oral prednisone, (ii) seven plasma exchanges, (iii) seven intravenous infusions of polyvalent immunoglobulin after each plasma exchange (0.1 g/kg, except the last at 1 g/kg), and (iv) one rituximab injection (375 mg/m 2) on day 14. Azathioprine was switched for mycophenolate mofetil given its additional anti-B-cell properties. DSA were controlled negative and arterial oxygen pressure improved, oxygen therapy was stopped. Mycoplasma pneumonia serology, initially negative (IgG = 2.5 UI/mL, IgM <8.5 UI/mL), was positive on day 14 (IgG 15.8 UI/mL, IgM <8.5 UI/mL). At day 20 and month 3, computed tomography was still improving [Figure 1]b and [Figure 1]c. Unfortunately 6 months after the episode, she developed a bronchiolitis obliterans syndrome (BOS) with a dependence to noninvasive ventilator. Retransplantation was decided and 1 year later, she is still on the waiting list with a grades three BOS.
Figure 1: Computed tomography showing at day 1 (a) diffuse bilateral ground glass opacities with thickened septal lines, improved at day 20 (b) and month 3 (c) after antibiotics, corticosteroids, plasmapheresis, intravenous immunoglobulin, and rituximab

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   Discussion Top

We report a case of severe Mycoplasma pneumoniae pneumonia, inducing an acute pulmonary AMR with favorable outcome following antibiotics and early aggressive immunosuppressive therapy.

The clinical presentation without trimethoprim-sulfamethoxazole prophylaxis in such immunocompromised host was initially suggestive of Pneumocystis jirovecii pneumonia, but this diagnosis was ruled out by negative BAL including specific PCR. As the detection of M. pneumoniae in respiratory tract could just reflect a colonization,[1] beta-lactam antibiotics were continued until the confirmation of the diagnosis. Here, the diagnosis of M. pneumoniae pneumonia can be assessed by a 4-fold increase in IgG antibodies titers in serum and detection of bacteria in the lower respiratory tracts by PCR [2] despite the lack of positive culture.[3] However, despite the administration of a macrolide antibiotic, the respiratory insufficiency, and the inflammatory syndrome did not improve after 3 days. Thus, in the context of recent modification of immunosuppression regimen and detection of DSA, possible AMR [4] was considered although diagnosed lately after transplantation.[5] Indeed, in lung transplantation, the process of allorecognition is likely to be augmented by local innate immune activation through endogenous tissue injury and exogenous infection.[5] Cases of acute rejection after infectious pneumonia had already been observed.[6] Thus, the interaction between infectious pathogens and acute AMR should be further studied. In particular, this is currently increasing evidence for relationship between BOS and Pseudomonas or Aspergillus infection and/or colonization.[7],[8]

The development of DSA has been linked to an increased risk of acute rejection and BOS.[9],[10] Experimental studies suggest that HLA antibodies have a pathogenic role and are not merely an epiphenomenon of humoral immunity.[11] Thus, one can speculate that early antibody depletion may favorably influence clinical outcome as suggested by the current case report. The patients who developed DSA and received antibody-directed therapy had a similar incidence of acute rejection and BOS as those who did not develop DSA; moreover, patients with successful depletion of DSA had greater freedom from BOS and better survival than those who had persistent DSA.[12] However, clinical evolution of AMR is sometimes severe as reported in a retrospective study where plasmapheresis, rituximab, and intravenous immunoglobulin were only administered for patients with declining allograft function.[13] Whatever, a single episode of acute rejection, as well as increased frequency and severity of acute rejection, increases the risk for BOS.[14]

This case emphasizes the interest to detect donor-specific antibodies in atypical or severe respiratory disorder in lung transplant recipients. Specific immunosuppressive therapy should be promptly started and is likely to decrease the risk of BOS. However, concomitant infections should always be investigated using a large panel test because the clinical presentation could be severe and atypical in such immunocompromised patients.


We would like to thank the patient, for allowing the publication of the document, Valérie Dubois from the French Blood Bank, Helene Morisse-Pradier, Soazic Grard, Gael Bourdin, François Philit for clinical expertise, nurses of the Louis-Pradel, and Croix-Rousse hospitals involved in the care of the patient.

Financial support and sponsorship

JFM reports receiving consulting fees, grants, lecture fees, or travel support from LFB Biomédicaments, CSL Behring, Actelion, Boehringer Ingelheim, Pfizer, GSK, Chiesi, Bayer, Bioprojet, and MSD. SD, JS, and AS report no financial link.

Conflicts of interest

There are no conflicts of interest.

   References Top

Spuesens EB, Fraaij PL, Visser EG, Hoogenboezem T, Hop WC, van Adrichem LN, et al. Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: An observational study. PLoS Med 2013;10:e1001444.  Back to cited text no. 1
Kashyap S, Sarkar M. Mycoplasma pneumonia: Clinical features and management. Lung India 2010;27:75-85.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
Vishak A, Rameschandra S, Shalini SM, Sunil A, Arnand R. Study of isolation of Mycoplasma pneumoniae in asthmatics by sputum culture. Lung India 2005;22:50-3.  Back to cited text no. 3
Levine DJ, Glanville AR, Aboyoun C, Belperio J, Benden C, Berry GJ, et al. Antibody-mediated rejection of the lung: A consensus report of the international society for heart and lung transplantation. J Heart Lung Transplant 2016;35:397-406.  Back to cited text no. 4
Martinu T, Chen DF, Palmer SM. Acute rejection and humoral sensitization in lung transplant recipients. Proc Am Thorac Soc 2009;6:54-65.  Back to cited text no. 5
Garantziotis S, Howell DN, McAdams HP, Davis RD, Henshaw NG, Palmer SM. Influenza pneumonia in lung transplant recipients: Clinical features and association with bronchiolitis obliterans syndrome. Chest 2001;119:1277-80.  Back to cited text no. 6
Weigt SS, Copeland CA, Derhovanessian A, Shino MY, Davis WA, Snyder LD, et al. Colonization with small conidia Aspergillus species is associated with bronchiolitis obliterans syndrome: A two-center validation study. Am J Transplant 2013;13:919-27.  Back to cited text no. 7
Gregson AL, Wang X, Weigt SS, Palchevskiy V, Lynch JP 3rd, Ross DJ, et al. Interaction between Pseudomonas and CXC chemokines increases risk of bronchiolitis obliterans syndrome and death in lung transplantation. Am J Respir Crit Care Med 2013;187:518-26.  Back to cited text no. 8
Lobo LJ, Aris RM, Schmitz J, Neuringer IP. Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation. J Heart Lung Transplant 2013;32:70-7.  Back to cited text no. 9
Palmer SM, Davis RD, Hadjiliadis D, Hertz MI, Howell DN, Ward FE, et al. Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome. Transplantation 2002;74:799-804.  Back to cited text no. 10
Jaramillo A, Smith CR, Maruyama T, Zhang L, Patterson GA, Mohanakumar T. Anti-HLA class I antibody binding to airway epithelial cells induces production of fibrogenic growth factors and apoptotic cell death: A possible mechanism for bronchiolitis obliterans syndrome. Hum Immunol 2003;64:521-9.  Back to cited text no. 11
Hachem RR, Yusen RD, Meyers BF, Aloush AA, Mohanakumar T, Patterson GA, et al. Anti-human leukocyte antigen antibodies and preemptive antibody-directed therapy after lung transplantation. J Heart Lung Transplant 2010;29:973-80.  Back to cited text no. 12
Otani S, Davis AK, Cantwell L, Ivulich S, Pham A, Paraskeva MA, et al. Evolving experience of treating antibody-mediated rejection following lung transplantation. Transpl Immunol 2014;31:75-80.  Back to cited text no. 13
Sharples LD, McNeil K, Stewart S, Wallwork J. Risk factors for bronchiolitis obliterans: A systematic review of recent publications. J Heart Lung Transplant 2002;21:271-81.  Back to cited text no. 14


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